Pharmaceutical compositions utilizing 2-amino-1,4-dihydropyridine derivatives and method of effecting coronary vessel dilation and treating hypertension in humans and animals utilizing said compounds

ABSTRACT

2-Amino-1,4-dihydropyridines bearing a carbonyl function in the 5-position and being optionally substituted by lower alkyl or phenyl in the 6-position, and the corresponding 2-amino1,4,5,6,7,8-hexahydro-5-oxoquinolines, which derivatives are further substituted by a carbonyl group in the 3-position and optionally substituted in the 4-position by lower alkyl, phenyl, substituted phenyl or a heterocylic group are antihypertensive agents and coronary vessel dilators. The compounds, of which 2amino-6-methyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5dicarboxylic acid 3,5-diethyl ester is a representative embodiment, are prepared through condensation of an ylideneacetoacetic acid ester and an amidine.

Meyer et al. Oct. 7, 1975 I54] PHARMACEUTICAL COMPOSITIONS [58] Field ofSearch 424/256, 251, 226

UTILIZING Z-AMINO-l,4-DIHYDROPYRIDINE [56} References Cited DERIVATIVESAND METHOD OF UNITED STATES PATENTS EFFECTING CORONARY VESSEL 3,511,8475/1970 Love 260/2955 R DILATION AND TREATING 3,696,112 10/1972 Bossertet al, H 260/2955 R HYPERTENSION IN HUMANS AND ANIMALS UTILIZING SAIDCOMPOUNDS Inventors: Horst Meyer; Friedrich Bossert,

both of Wuppertal-Elberfeld; Wulf Vater, Opladen; Kurt Stoepel,Wuppertal-Elberfeld, all of Germany Assignee: Bayer Aktiengesellschaft,Germany Filed: Feb. 4, I974 App]. No; 439,305

Related US. Application Data Division of Ser. No. 336,639, Feb. 28,1973.

Foreign Application Priority Data Apr. 14, 1973 Germany 2210674 US. Cl424/226; 424/256 Int. Cl. A61K 31/655; A6IK 3l/435 PrimaryExamz'nerAlbert T, Meyers Assistant Examz'nerDaren M. Stephens [57]ABSTRACT 2-Amino-l,4-dihydropyridines bearing 21 carbonyl function inthe 5-position and being optionally substituted by lower alkyl or phenylin the 6-position, and the correspondingZ-amino-l,4,5,6,7,8-hexahydro-5- oxoquinoiines, which derivatives arefurther substituted by a carbonyl group in the 3-position and 0ptionally substituted in the 4-position by lower alkyl, phenyl,substituted phenyl or a heterocylic group are antihypertensive agentsand coronary vessel dilators. The compounds, of which2-amino-6-methyl-4-(3- nitrophenyl l ,4-dihydropyridine-3,5-dicarboxylic acid 3,5-diethyl ester is a representative embodiment,are prepared through condensation of an ylideneacetoacetic acid esterand an amidine.

I76 Claims, No Drawings PHARMACEUTICAL COMPOSITIONS UTILIZING Z-AMINO-1,4-DII-IYDROPYRIDINE DERIVATIVES AND METHOD OF EFFECI'ING CORONARYVESSEL DILATION AND TREATING HYPERTENSION IN HUMANS AND ANIMALSUTILIZING SAID COMPOUNDS This is a division of application Ser. No.336,639 filed Feb. 28, 1973.

DETAILED DESCRIPTION The present invention pertains to 2-amino-l,4-dihydropyridine derivaties, to processes for their production and useand to pharmaceutical compositions containing such compounds and usefulas antihypertensive agents and coronary vessel dilators.

In particular, the present invention pertains to con-I- pounds of theformula wherein R is hydrogen; lower alkyl, lower alkenyl; loweralkynyl; phenyl; substituted phenyl in which the substituents are one tothree members selected from the group consisting of lower alkyl, loweralkoxy, halogeno, nitro, cyano, trifluoromethyl, azido, carbo(loweralkoxy), lower alkylsulfonyl, lower alkylsulfinyl, lower alkylthio orphenyl', naphthyl; or a heterocyclic ring selected from the groupconsisting of quinolyl, isoquinolyl, pyridyl, pyrimidyl, thenyl, furyland pyrryl, said heterocyclic ring being unsubstituted or substituted byone or two members selected from the group consisting of lower alkyl,lower alkoxy and halogeno;

R, when taken independently, is hydrogen, lower a]- kyl, phenyl orpyridyl;

R when taken independently, is lower alkyl, lower alkoxy loweralkoxy(lower alkoxy), lower alkenyloxy, lower alkynyloxy, amino, loweralkylamino or di(lower alkyl)amino,

R and R when taken together are alkylene of 2 to 4 carbon atoms; and

R is lower alkyl, lower alkoxy, lower alkoxy(lower alkoxy), loweralkenyloxy, lower alkynyloxy, amino, lower alkylamino or di(loweralkyl)amino.

The term lower alkyl denotes a univalent saturated branched or straighthydrocarbon chain containing from l to 6 carbon atoms. Representative ofsuch lower alkyl groups are thus methyl, ethyl, propyl, isopropyl,butyl, isobutyl, sec.butyl, tert.butyl, pentyl, isopentyl, neopentyl,tert.pentyl, hexyl, and the like.

The term lower alkenyl denotes a univalent branched or straighthydrocarbon chain containing from 2 to 6 carbon atoms and nonterminalethylenic unsaturation as, for example, vinyl, allyl, isopropenyl,2-butenyl, 3-methyl-2-butenyl, 2-pentenyl, 3-pentenyl, 2-hexenyl,4-hexenyl, and the like.

The term lower alkynyl denotes a univalent branched or straighthydrocarbon chain containing from 2 to 6 carbon atoms and nonterminalacetylenic unsaturation as, for example, ethynyl, 2-propynyl,4-pentynyl, and the like.

The term lower alkoxy denotes a straight or branched hydrocarbon chainbound to the remainder of the molecule through an ethereal oxygen atomas, for example, methoxy, ethoxy, propoxy, isopropoxy, butoxy,isobutoxy, pentoxy and hexoxy.

The term lower alkylthio denotes a branched or straight hydrocarbonchain bound to the remainder of the molecule through a divalent sulfuras, for example, methylthio, ethylthio, propylthio, isopropylthio,butylthio, and the like.

The term halogen denotes the substituents fluoro, chloro, bromo andiodo.

As indicated, the present invention also pertains to the physiologicallyacceptable non-toxic acid addition salts of these basic compounds. Suchsalts include those derived from organic and inorganic acids such as,without limitation, hydrochloric acid, hydrobromic acid, phosphoricacid, sulfuric acid, methane sulphonic acid, acetic acid, tartaric acid,lactic acid, succinic acid, citric acid, malic acid, maleic acid, sorbicacid, aconitic acid, salicylic acid, phthalic acid, embonic acid,enanthic acid, and the like.

According to the present invention, the foregoing compounds are preparedby reacting a dicarbonyl compound of the formula:

I C OR wherein R, R and R are as herein defined, with an amidine of theformula:

in which R is as herein defined. The condensation proceeds smoothly ingood yields simply by heating the two components, generally in thepresence of an inert organic solvent such as methanol, ethanol, propane]and similar alkanols, ethers such as dioxane and diethyl ether, glacialacetic acid, pyridine, dimethylformamide, dimethylsulfoxide,acetonitrile and the like. The reaction is conducted at temperatures offrom 20 to 250C, conveniently at the boiling point of the solvent, andwhile elevated pressure may be utilized, normal atmospheric pressure isgenerally satisfactory. The reactants are employed in substantiallyequimolar amounts. The amidine reactant can be employed as the free baseor in the form of a salt such as the hydrohalide salts with the amidinebeing liberated from the salt through treatment with a basic agent suchas an alkali metal alkoxide. The dicarbonyl reagent can be utilized assuch or generated in situ by the reaction of an aldehyde of the formulaRCI-[O and a B-dicarbonyl compound of the formula RCOCH COR [t is rathersurprising that the above described condensation produces the desiredcompounds in such good yields and with such high purity for while it isknown that a benzylideneacetoacetic acid ester can be condensed with anamino crotonic acid ester to yield a 1,4-dihydropyridine (Knoevenagel,Ber. 31, 743, 1898), it would be expected from, for example,Silversmith, Org. Chem. l7, 4090 1952) that the addition of an amidineto an a, B-unsaturated keto compound would yield the dihydropyrimidinederivative rather than the dihydropyridine derivative.

Many of the dicarbonyl compounds utilized as one of the reactants areknown to the art and the others can either be generated in situ asherein described or prepared according to methods well known to the art,see for example Org. Reaction XV, 204 et seq, (I967). Typical of thisreactant are the following compounds:

benzylideneacetoacetic acid methyl ester,

ethylideneacetoacetic acid methyl ester, isopropylideneacetoacetic acidmethyl ester, 2-nitrobenzylideneacetoacetic acid methyl ester,2-nitrobenzylideneacetylacetone, benzylideneacetylacetone,3-nitrobenzylideneacetoacetic acid methyl ester,

B-nitrobenzylideneacetoacetic acid propargyl ester,

3-nitrobenzylideneacetoacetic acid allyl ester,

3-nitrobenzylideneacetoacetic acid B-methoxyethyl ester,

3-nitrobenzylideneacetoacetic acid B-ethoxyethyl ester,

3-nitrobenzylideneacetoacetic acid isopropyl ester,

3-nitrobenzylideneacetylacetone,

4-nitrobenzylideneacetylacetone, 4 nitrobenzylideneacetoacetic acidB-propoxyethyl ester,

4-nitrobenzylideneacetoacetic acid n-propyl ester,

3-nitro-6-chlorobenzylideneacetoacetic acid methyl ester,

2-cyanobenzylideneacetoacetic acid methyl ester,

2-cyanobenzylideneacetoacetic acid methyl ester,

2-cyanobenzylideneacetoacetic acid ethyl ester,

2-cyanobenzylidenepropionylacetic acid ethyl ester,

3-cyanobenzylideneacetoacetic acid methyl ester,

3-nitro-4-chlorobenzylideneacetylacetone,

3-nitro-4-chlorobenzylideneacetoacetic acid t-butyl ester,

3-nitro-4-chlorobenzylideneacetoacetic acid methyl ester,

Z-nitro-4-methoxybenzylideneacetoacetic methyl ester,

Z-cyano-4-methylbenzylideneacetoacetic acid ethyl ester,

2-azidobenzylideneacetoacetic acid ethyl ester,

3-azid0benzylideneacetylacetone,

2-methylmercaptobenzylideneacetoacetic acid isopropyl ester,

2-sulphinylmethylbenzylideneacetoacetic acid ethyl ester,

2-sulphonylbenzylidenemethylacetoacetic acid allyl ester,

4-sulphonylmethylbenzylideneacetoacetic acid ethyl ester,

naphth-l-ylideneacetoacetic acid methyl ester,

naphth-l-ylideneacetoacetic acid ethyl ester,

naphth-2-ylideneacetoacetic acid ethyl ester,

Z-ethoxynaphth-l-ylideneacetoacetic acid methyl esacid ter,

2-methoxynaphthl -ylideneacetoacetic acid ethyl ester,

5bromonaphthl -ylideneacetoacetic acid methyl ester,

quinol 2-ylmethylideneacetoacetic acid methyl ester,

quinol-3-ylmethylideneacetoacetic acid methyl ester,

quinol-4-ylmethylideneacetoacetic acid ethyl ester,

quinol-8-ylmethylideneacetoacetic acid ethyl ester,

isoquinol-l-ylmethylideneacetoacetic acid methyl ester,

isoquinol-3-ylmethylideneacetoacetic acid methyl ester,

a-pyridylmethylideneacetoacetic acid methyl ester,

a-pyridylmethylideneacetoacetic acid ethyl ester,

a-pyridylmethylideneacetoacetic acid allyl ester,

a-pyridylmethylideneacetoacetic acid cyclohexyl ester,

B-pyridylmethylideneacetoacetic acid B-methoxyethyl ester,

'y-pyridylmethylideneacetoacetic acid methyl ester,

6-methyl-a-pyridylmethylideneacetoacetic acid ethyl ester,

4,6-dimethoxypyrimid-5-ylmethylideneacetoacetic acid ethyl ester,

then-2-ylmethylideneacetoacetic acid ethyl ester,

fur-2-ylmethylideneacetoacetic acid allyl ester,

pyrr-2-ylthylideneacetoacetic acid methyl ester,

nitrobenzylidenepropionylacetic acid ethyl ester,

a-pyridylmethylidenepropionylacetic acid ethyl ester,

a-pyridylmethylidenepropionylacetic acid methyl ester,

oz-pyridylmethylideneacetylacetone,

2-, 3- or 4-meth0xybenzylideneacetoacetic acid ethyl ester,

2-, 3- or 4-methoxybenzylideneacetylacetone,

2-meth0xybenzylideneacetoacetic acid allyl ester,

2-methoxybenzylideneacetoacetic acid allyl ester,

2-methoxybenzylideneacetoacetic acid propargyl ester,

2-methoxybenzylideneacetoacetic acid B-methoxyethyl ester,

2-isopropoxybenzylideneacetoacetic acid ethyl ester,

3-butoxybenzylideneacetoacetic acid methyl ester,

3,4,S-trimethoxybenzylideneacetoacetic acid allyl ester,

2-methylbenzylidenepropionylacetic acid methyl ester,

2-, 3- or 4-methylbenzylideneacetoacetic acid ethyl ester,

Z-methylbenzylideneacetoacetic acid B-methoxyethyl ester,

2-methylbenzylideneacetoacetic acid B-propoxyethyl ester,

Z-methylbenzylideneacetylacetone,

3,4-dimethoxy-5-brom0benzylideneacetoacetic acid ethyl ester,

2-, 3- or 4-chlorobenzylideneacetoacetic acid ethyl ester,

2-, 3- or 4-bromobenzylideneacetoacetie acid ethyl ester,

2-, 3- or 4-fluorobenzylideneacetoacetic acid ethyl ester,

Z-fluorobenzylideneacetoacetic acid methyl ester,

3-chlorobenzylideneacetylacetone,

3-chlorobenzylidenepropionylacetic acid ethyl ester,

3-chlorobenzylideneacetoacetic acid ethyl ester,

2-chlorobenzylideneacetoacetic acid allyl ester,

2-, 3- or 4-trifluoromethylbenzylideneacetoacetic acid isopropyl ester,

3-trifluoromethylbenzylideneacetoacetic acid methyl ester,

2-carbethoxybenzylideneacetoacetic acid ethyl ester,

3-carbomethoxybenzylideneacetoacetic acid methyl ester,

4-carboisopropoxybenzylideneacetoacetic acid isopropyl ester,4-carbomethoxybenzylideneacetoacetic acid allyl ester,

3-nitrobenzylidenecyclohexane-l ,3-dione, and

3-nitrobenzylidenecycloheptane-1 ,3-dione.

The amidine reactants are similarly known or can be readily producedaccording to known methods, see for example McElvain et al., J.A.C.S.,73, 2760 (l95l Typical of these reactants are the following:

amidinoacetic acid methyl ester,

amidinoacetic acid ethyl ester,

amidinoacetic acid n-propyl ester,

amidinoacetic acid isopropyl ester,

amidinoacetic acid cyclohexyl ester,

amidinoacetic acid B-methoxyethyl ester,

amidinoacetic acid a-ethoxyethyl ester,

amidinoacetic acid B-ethoxyethyl ester, amidinoacetic acid propargylester, and amidinoacetamide.

As noted above, the compounds of the present invention demonstrate theability to reduce blood pressure and to effect a dilation of thecoronary vessels. They can accordingly be used where either or both ofthese effects are desired. Thus upon parenteral, oral or sublingualadministration, the compounds produce a distinct and long lastingdilation of the coronary vessesl which is intensified by a simultaneousnitrite-like effect of reducing the load on the heart. The effect onheart metabolism is thus one of energy saving. In addition. thecompounds lower the blood pressure of normotonic and hypertonic animalsand can thus be used as antihypertens'ive agents. These properties canbe conveniently observed in well known laboratory models. Thus forexample the coronary vessel dilation effect can be observed by measuringthe increase in oxygen saturation in the coronary sinus in thenarcotized, heart catheterized dog, as shown in the following table:

4-( 3-nitrophcnyl l,4-dihydropyridine-3,5 dicarb0xylic acid diethylester The hypotensive activity of the present compounds can be observedby measuring the blood pressure of hypertensive rats followingadministration of the compounds. The following table demonstrates thedose which results in at least a l5 mm Hg reduction in blood pressure ofsuch animals:

Compound Dose (mg/kg] 2-amino-6-rnethyl-4phenyll ,4- l .0dihydropyridine-3,S-dicarboxylic acid diethyl ester 2-amino 6-methyl-4-(2-nitrophenyl ,4-dihydropyridine-3,S-dicarboxylic acid 3-ethyl esterS-methyl ester 2-ami no-6- methyl 4-( 2-methoxyphenyl l,4-dihydropyridine 3 ,S-dicarboxylic acid diethyl ester2-amino-6-methyl-4-( Z-cyanophenyl l ,4 dihydropyridine-3,S-dicarboxylicacid diethyl ester 2-amino6 methyl -4-( Z-trifluoromethylphenyl l ,4dihydropyridine-3,5dicar boxylic acid diethyl ester2-amino-fi-methyl-4-( 3-nitrophenyl l ,4-dihydropyridine-3.5'dicarboxylic acid diethyl ester 2-amino-6-methyl-4-(3-nitrophenyl l ,4- dihydropyridine-3,S-dicarboxylic acid 3-ethyl esterS-methyl ester 2-amino-6-methyl-4-( 3-nitrophenyl l ,4-dihydropyridine-3,S-dicarboxylic acid S-ethyl ester S-B-methoxyethylester Z-amino-5-acetyl-6-methy|-4-( 3-nitrophenyl l ,4-dihydropyridine-3'carboxylic acid ethyl ester 2amino-6-methyl-4( 3-nitro-6-chlorophenyl)-l ,4-dihydropyridinc-3,5dicarboxylic acid 3-ethyl ester S-methyl esterThe toxicity of the compounds is remarkably low. Thus for example thetoxic dose of Z-amino-G-methyl- 4-( 2-trifl uoromethylphenyl l,4-dihydropyridine-3 ,5 dicarboxylic acid diethyl ester in mice uponoral administration is greater than 1000 mg/kg.

In addition to the effect on blood pressure and coronary vessels, thecompounds also lower the excitability of the stimulus formation andexcitation conduction system within the heart so that anantifibrillation action is observed at therapeutic doses. The tone ofthe smooth muscle of the vessels is also greatly reduced. Thisvascular-spasmolytic action can be observed in the entire vascularsystem as well as in more or less isolated and circumscribed vascularregions such as the central nervous system. In addition, a strongmuscularspasmolytic action is manifested in the smooth muscle of thestomach. the intestinal tract, the urogenital tract and the respiratorysystem. Finally, there is some evidence that the compounds influence thecholesterol level and lipid level of the blood. These effects complementone another and the compounds are thus highly desirable aspharmaceutical agents to be used in the treatment of hypertension andconditions characterized by a constriction of the coronary bloodvessels.

Pharmaceutical compositions for effecting such treatment will contain amajor or minor amount, e.g. from to 0.5%, of at least one 2-amino-1,4-dihydropyridine as herein defined in combination with a pharmaceuticalcarrier, the carrier comprising one or more solid, semi-solid or liquiddiluent, filler and formulation adjuvant which is nontoxic, inert andpharmaceutically acceptable. Such pharmaceutical compositions arepreferably in dosage unit form; i.e. physically discrete unitscontaining a predetermined amount of the drug corresponding to afraction or multiple of the dose which is calculated to produce thedesired therapeutic response. The dosage units can contain one, two,three four or more single doses or, alternatively, one-half, third orfourth of a single dose. A single dose preferably contains an amountsufficient to produce the desired therapeutic effect upon administrationat one application of one or more dosage units according to apredetermined dosage regimen, usually a whole, half, third or quarter ofthe daily dosage administered once, twice, three of four times a day.Other therapeutic agents can also be present.

Although the dosage and dosage regimen must in each case be carefullyadjusted, utilizing sound professional judgment and considering the age,weight and condition of the recipient, the route of administration andthe nature and gravity of the illness, generally the daily dose will befrom about 0.001 to about 2 mg/kg, preferably 0.005 to 1.0 mg/kg, whenadministered parenterally and from about 0.1 to about mg/kg, preferably0.5 to 10 mg/kg, when administered orally. in some instances asufficient therapeutic effect can be obtained at lower doses while inothers, larger doses will be required.

Oral administration can be effected utilizing solid and liquid dosageunit forms such as powders, tablets, dragees, capsules, granulates,suspensions, solutions and the like.

Powders are prepared by comminuting the compound to a suitable fine sizeand mixing with a similarly comminuted pharmaceutical carrier such as anedible carbohydrate as for example starch, lactose, sucrose, glucose ormannitol. Sweetening, flavoring, preservative, dispersing and coloringagents can also be present.

Capsules are made by preparing a powder mixture as described above andfilling formed gelatin sheaths. Glidants and lubricants such ascolloidal silica, talc, magnesium stearate, calcium stearate or solidpolyethylene glycol can be added to the powder mixture before thefilling operation. A disintegrating or solubilizing agent such asagar-agar, calcium carbonate or sodium carbonate can also be added toimprove the availability of the medicament when the capsule is ingested.

Tablets are formulated for example by preparing a powder mixture,granulating or slugging, adding a lubricant and disintegrant andpressing into tablets. A powder mixture is prepared by mixing thecompound, suitably comminuted, with a diluent or base as describedabove, and optionally with a binder such as carboxymethyl cellulose. analginate, gelatin, or polyvinyl pyrrolidone, a solution retardant suchas paraffin, a resorption accelerator such as a quaternary salt and/oran absorption agent such as bentonite, kaolin or dicalcium phosphate.The powder mixture can be granulated by wetting with a binder such assyrup, starch paste, acacia mucilage or solutions of cellulosic orpolymeric materials and forcing through a screen. As an alternative togranulating, the powder mixture can be run through the tablet machineand the resulting imperfectly formed slugs broken into granules. Thegranules can be lubricated to prevent sticking to the tablet formingdies by means of the addition of stearic acid, a stearate salt, talc ormineral oil. The lubricated mixture is then compressed into tablets. Themidicaments can also be combined with free flowing inert carriers andcompressed into tablets directly without going through the granulatingor slugging steps. A clear or opaque protective coating consisting of asealing coat of shellac, a coating of sugar or polymeric material and apolish coating of wax can be provided. Dyestuffs can be added to thesecoatings to distinguish different unit dosages.

Oral fluids such as solutions, syrups and elixirs can be prepared indosage unit form so that a given quantity contains a predeterminedamount of the compound. Syrups can be prepared by dissolving thecompound in a suitably flavored aqueous sucrose solution while elixirsare prepared through the use of a nontoxic alcoholic vehicle.Suspensions can be formulated by dispersing the compound in a nontoxicvehicle. Solubilizers and emulsifiers such as ethoxylated isostearylalcohols and polyoxyethylene sorbitol esters, preservatives, flavoradditives such as peppermint oil or saccharin, and the like can also beadded.

Where appropriate, dosage unit formulations for oral administration canbe microencapsulated. The formulation can also be prepared to prolong orsustain the release as for example by coating or embedding particulatematerial in polymers, wax or the like.

Parenteral administration can be effected utilizing liquid dosage unitforms such as sterile solutions and suspensions intended forsubcutaneous, intramuscular or intravenous injection. These are preparedby suspending or dissolving a measured amount of the compound in anontoxic liquid vehicle suitable for injection such as an aqueous oroleaginous medium and sterilizing the suspension or solution.Alternatively a measured amount of the compound is placed in a vial andthe vial and its contents are sterilized and sealed. An accompanyingvial or vehicle can be provided for mixing prior to administration.Nontoxic salts and salt solutions can be added to render the injectionisotonic. Sta bilizers, preservatives and emulsifiers can also be added.

The following examples will serve to further typify the nature of thepresent invention through the presentation of specific embodiments.These examples should not be construed as a limitation on the scope ofApplicants invention since the subject matter regarded as the inventionis set forth in the appended claims.

EXAMPLE 1 Upon boiling a solution of 21.8 g of benzylideneacetoaceticacid ethyl ester and 13.0 g of amidinoacetic acid ethyl ester in 150 mlof ethanol for 2 hours, 2- amino-6-methyl-4-pheny1- l,4-dihydropyridine-3 ,5- dicarboxylic acid diethyl ester of meltingpoint 164C (alcohol) is obtained.

Yield: 67% of theory.

EXAMPLE 2 Upon boiling a solution of 24.9 g of 2-nitrobenzylideneacetoacetic acid methyl ester and 13.0 g ofamidinoacetic acid ethyl ester in ml of ethanol for 1 hour.2-amino-6-methyl-4-( 2-nitrophenyl)-1,4-dihydropyridine-S,S-dicarboxylic acid 3-ethyl ester 5- methyl ester ofmelting point 168C (alcohol) is obtained.

Yield: 59% of theory.

EXAMPLE 3 Upon boiling a solution of 24.8 g of2methoxybenzylideneacetoacetic acid ethyl ester and 13.0 g ofamidinoacetic acid ethyl ester in ml of ethanol for 1 hour,2-amino-6-methyl 4-(2-methoxyphenyl)-1,4-dihydropyridine-3,S-dicarboxylic acid diethyl ester of melting point170C (ethanol) is obtained.

Yield: 65% of theory.

EXAMPLE 4 Upon boiling a solution of 23.2 g of2-methylbenzylideneacetoacetic acid ethyl ester and 13.0 g ofamidinoacetic acid ethyl ester in 150 ml of ethanol for 2 hours,2-amino-6-methyl-4-(2-methylphenyl)-l,4-dihydropyridine-3,S-dicarboxylic acid diethyl ester of melting point130C (ethanol) is obtained.

Yield: 71% of theory.

EXAMPLE 5 Upon boiling a solution of 24.3 g of 2-cyanobenzylideneacetoacetic acid ethyl ester and 13.0 g of amidinoaceticacid ethyl ester in 100 ml of ethanol for 2 hours,2-amino-6-methyl-4(2-cyanophenyl)-l,4- dihydropyridine-3,5-dicarboxylicacid diethyl ester of melting point 208C (ethanol) is obtained.

Yield: 54% of theory.

EXAMPLE 6 EXAMPLE 7 Upon boiling aa solution of 12.6 g of 3-chlorobenzylideneacetoacetic acid ethyl ester and 6.5 g of amidinoaceticacid ethyl ester in 100 ml of ethanol for 2 hours,2-amino-6-methyl-4-(3-ch1orophenyl)- 1 ,4dihydropyridine-3,S-dicarboxylic acid diethyl ester of melting point 157159C (ethanol) is obtained. Yield: 62% of theory.

EXAMPLE 8 Upon boiling a solution of 13.2 g of4-methylmercaptobenzylideneacetoacetic acid ethyl ester and 6.5 g ofamidinoacetic acid ethyl ester in 100 ml of ethanol for 1 hour,2-amino-6-methyl-4-( 4- methylmercaptophenyl 1 ,4-dihydropyridine-3 ,5-dicarboxylic acid diethyl ester of melting point 165C (ethylacetate/petroleum ether) is obtained.

Yield: 49% of theory.

EXAMPLE 9 Upon boiling a solution of 26.3 g of 3-nitrobenzylideneacetoacetic acid ethyl ester and 13.0 g of amidinoaceticacid ethyl ester in 200 ml of ethanol for 1 hour,2-amino-6-methyl-4-(3-nitrophenyl)-1,4- dihydropyridine 3,5-dicarboxylicacid diethyl ester of melting point 169C (ethanol) is obtained.

Yield: 58% of theory.

EXAMPLE 10 Upon boiling a solution of 24.9 g of 3-nitrobenzylideneacetoacetic acid methyl ester and 13.0 g ofamidinoacetic acid ethyl ester in 180 ml of ethanol for 1 hour,2-amino-6-methyl-4-( 3-nitrophenyl)-1,4-dihydropyridine-3,S-dicarboxylic acid 3-ethyl ester 5- methyl ester ofmelting point 124C is obtained. Yield: 59% of theory.

EXAMPLE 11 Upon heating a solution of 13.8 g of 3-nitrobenzylideneacetoacetic acid isopropyl ester and 6.5 g ofamidinoacetic acid ethyl ester in 150 ml of ethanol for 2 hours,2-amino-6-methyl-4-(3-nitrophenyl)- 1,4-dihydropyridine-3,5-dicarboxylicacid 3-ethyl 5- isopropyl ester of melting point 206 207C (alcohol) isobtained.

Yield: 62% of theory.

EXAMPLE 1 2 Boiling a solution of 10.9 g of 3-nitrobenzylideneacetoacetic acid propargyl ester and 5.2 g ofamidinoacetic acid ethyl ester in ml of ethanol for 1 hour yields2-amino-6-methyl-4-( 3- nitrophenyl )-1 ,4-dihydropyridine-3,S-dicarboxylic acid 3-ethyl ester S-propargyl ester of melting point181C (ethanol).

Yield: 59% of theory.

EXAMPLE 1 3 Heating a solution of 14.6 g of 3-nitrobenzylideneacetoacetic acid B-methoxyethyl ester and 6.5 g ofamidinoacetic acid ethyl ester in ml of ethanol for 1 hour yields2-amino-6-methyl-4-(3- nitrophenyl)-1 ,4-dihydropyridine-3,S-dicarboxylic acid 3-ethyl ester S-B-methoxyethyl ester of meltingpoint 179C (ethyl acetate/petroleum ether).

Yield: 58% of theory.

EXAMPLE 14 Upon boiling a solution of 7.6 g of 3- nitrobenzaldehyde, 5.0g of acetylacetone and 6.5 g of amidinoacetic acid ethyl ester in 100 mlof ethanol for 2 hours, 2-amino-5-acetyl-6methyl-4-( 3-nitrophenyl)-1,4-dihydropyridine-3-carboxylic acid ethyl ester of melting point 217C(ethanol) is obtained.

Yield: 48% of theory.

EXAMPLE 15 Upon boiling a solution of 14.2 g of 3-nitro-6-chlorobenzylideneacetoacetic acid methyl ester and 6.5 g ofamidinoacetic acid ethyl ester in 100 ml of ethanol for 1 hour,2-amino-6-methyl-4-(3-nitro-6- chlorophenyl )-l,4-dihydropyridine-3,S-dicarboxylic acid 3-ethyl ester 5methy1 ester ofmelting point 124C (ethanol) is obtained.

Yield: 73% of theory.

EXAMPLE 16 Upon boiling a solution of 10.4 g of 2-furfurylideneacetoacetic acid ethyl ester and 6.5 g of amidinoaceticacid ethyl ester in 100 ml of ethanol for 2 hours,2-amino-6-methyl-4-(fur-Z-yl)-1,4- dihydropyridine-3,S-dicarboxylic aciddiethyl ester of melting point 183C (isopropanol) is obtained.

Yield: 78% of theory.

EXAMPLE 1 7 Upon boiling a solution of 14.0 g ofbenzylidenebenzoylacetic acid ethyl ester and 6.5 g of amidinoaceticacid ethyl ester in 150 ml of ethanol for 2 hours, 2-amino-4,6-diphenyl- 1 ,4-dihydropyridine-3,5 dicarboxylic acid ethylester of melting point 183C (ethanol) is obtained.

Yield: 48% of theory.

EXAMPLE 18 Upon heating a solution of 15.6 g of ethylideneacetoaceticacid ethyl ester and 13.0 g of amidinoacetic acid ethyl ester in 100 mlof ethanol for 2 hours, 2-amino-4,6-dimethyl-l,4-dihydropyridine-3,5-dicarboxylic acid diethyl ester of melting point 140C (isopropanol)is obtained.

Yield: 59% of theory.

EXAMPLE 19 Upon boiling a solution of 2.8 g of acetaldehyde, 5.6 g ofcyclohexanel ,3-dione and 6.5 g of amidinoacetic acid ethyl ester in 100ml of ethanol for 2 hours, 2amino-4-methyll,4,5,6,7,S-hexahydro-S-oxoquinoline-3- carboxylic acid ethyl ester ofmelting point 236C (ethanol) is obtained Yield: 53% of theory.

EXAMPLE 20 Upon boiling a solution of 7.6 g of 3- nitrobenzaldehyde, 5.6g of cyclohexane-1,3-dione and 6.5 g of amidinoacetic acid ethyl esterfor 1 hour, 2- arnino-4-(3-nitrophenyl)-1,4,5,6,7,8-hexahydro-5-oxoquinoline-3-carboxylic acid ethyl ester of melting point 260C isobtained (alcohol/DMF).

Yield: 61% of theory.

EXAMPLE 21 Upon boiling a solution of 7.1 g of 3 chlorobenzaldehyde. 5.6g of cyclohexane-l,3-dione and 6.5 g of amidinoacetic acid ethyl esterin 150 ml of ethanol for 2 hours, 2-amino-4-(3-chlorophenyl)- 1,4,5,6,7,8-hexahydro-5-oxoquinoline-3-carboxylic acid ethyl ester of meltingpoint 266C (ethanol/DMF) is obtained.

Yield: 66% of theory.

EXAMPLE 22 Upon boiling a solution of 5.3 g of pyridin-2 aldehyde, 5.6 gof cyclohexane-l,3-dione and 6.5 g of amidinoacetic acid ethyl ester in150 ml of alcohol for 3 hours,2-amino-4-(a-pyridyD-1,4,5,6,7,8-hexahydro- 5-oxoquinoline-3-carboxylicacid ethyl ester of melting point 260C is obtained (alcohol).

Yield: 46% of theory.

EXAMPLE 23 Upon heating a solution of 7.6 g of 2- nitrobenzaldehyde, 5.6g of cyclohexane-l,3-dione and 6.5 g of amidinoacetic acid ethyl esterin 100 ml of ethanol for 2 hours, 2-amino-4-(2-nitrophenyl)-l,4,5.6,7,8-hexahydro-5-oxoquinoline-3-carboxylic acid ethyl ester ofmelting point 212C (alcohol) is obtained.

Yield: 69% of theory.

EXAMPLE 24 EXAMPLE 25 Upon boiling a solution of 5.7 g of 4,6-dimethoxypyrimidin-S-aldehyde, 3.8 g of cyclohexane- 1,3-dione and 4.4 gof amidinoacetic acid ethyl ester in ml of ethanol for 8 hours,2-amino-4-(4,6- dimethoxypyrimid-S-yl 1 ,4,5,6, 7,8-hexahydro-5-oxoquinoline-3-carboxylic acid ethyl ester of melting point 273C(alcohol) is obtained.

Yield: 65% of theory.

EXAMPLE 26 Upon boiling a solution of 6.3 g of l-naphthaldehyde, 4.5 gof cyclohexane-1,3-dione and 5.2 g of amidinoacetic acid ethyl ester in150 ml of ethanol for 2 hours, 2-amino-4-(naphth- 1 -y1 l,4,5,6,7,8-hexahydro-5- oxoquinoline-3-carboxylic acid ethyl ester ofmelting point 279C (ethanol/DMF) is obtained.

Yield: 64% of theory.

EXAMPLE 27 Upon heating a solution of 6.3 g of isoquinolin-laldehyde,4.5 g of cyclohexane-l ,3-dione and 5.2 g of amidinoacetic acid ethylester in ml of ethanol for 2 hours,2-amino-4-(isoquinol-l-yl)-1,4,5,6,7,8-hexahydro-S-oxoquinoline-3-carboxylic acid ethyl ester of melting point272C (ethanol) is obtained.

EXAMPLE 28 Upon heating a solution of 4.8 g of 6-methylpyridin-2-aldehyde, 4.5 g of cyclohexane-l,3-dione and 5.2 g of amidinoaceticacid ethyl ester in ml of ethanol for 8 hours, 2-amino-4-(6-methylpyrid-2-yl 1,4,5 ,6,7,8-hexahydro-5-oxoquinoline-3-carboxylicacid ethyl ester of melting point 260C (ethanol/DMF) is obtained. Yield:46% of theory.

EXAMPLE 29 Upon boiling a solution of 13.3 g of 3-nitrobenzylideneacetoacetic acid ethyl ester and 5.1 g ofamidinoacetamide in ml of ethanol for 2 hours, 2-amino-6-methyl-5-carbethoxy-4-( 3-nitrophenyl 1,4--dihydropyridine-3-carboxylic acidamide of melting point 260C (alcohol) is obtained.

Yield: 52% of theory.

EXAMPLE 30 Upon heating a solution of 6.5 g of 2- cyanobenzaldehyde, 5.6g of cyclohexane-1,3-dione and 6.5 g of amidinoacetic acid ethyl esterin 100 ml of ethanol for 5 hours. 2-amino-4-(2-cyanophenyl)-1,4,5,6,7,8-hexahydro-5-oxoquinoline-3-carboxylic acid ethyl ester ofmelting point C (ethanol) is obtained.

Yield: 49% of theory.

EXAMPLE 31 Upon heating a solution of 26.3 g of 3-nitrobenzylideneacetoacetic acid ethyl ester and 14.4 g of amidinoaceticacid isopropyl ester in 250 ml of ethanol for 2 hours,2-amino-6-methyl-4-( 3-nitrophenyl)-1,4-dihydropyridine-3,S-dicarboxylic acid 3-isopropy1 ester 5-ethylester of melting point -6C (ethanol) is obtained.

Yield: 77% of theory.

EXAMPLE 32 EXAMPLE 33 Upon heating a solution of 13.9 g of 3-nitrobenzylideneacetoacetic acid isopropyl ester and 7.2 g ofamidinoacetic acid isopropyl ester in 180 ml of ethanol for 1 hour,2-amino-6-methyl-4-(3- nitrophenyl )-l,4-dihydropyridine-3,S-dicarboxylic acid diisopropyl ester of meltingpoint 122C (ether) is obtained. Yield: 62% of theory.

EXAMPLE 34 Upon boiling a solution of 12.2 g of 2-cyanobenzylideneacetoacetic acid ethyl ester and 7.2 g of amidinoaceticacid isopropyl ester in 200 ml of ethanol for 1 hour,2-amino-6-methy1-4-(2-cyanophenyl)- 1,4-dihydropyridine-3,S-dicarboxylicacid 3-isopropyl ester S-ethyl ester of melting point 200C (isopropanol)is obtained.

Yield: 58% of theory.

EXAMPLE 35 Upon heating a solution of 12.5 g of 3-nitrobenzylideneacetoacetic acid methyl ester and 7.2 g of amidinoaceticacid isopropyl ester in 150 ml of ethanol for 2 hours,2-amino-6-methyl-4-( 3-nitrophenyl)-l,4-dihydropyridine-3,S-dicarboxylic acid 3isopropyl ester S-methylester of melting point 167C (ethanol) is obtained.

Yield: 82% of theory.

EXAMPLE 36 Upon heating a solution of 1 1.0 g of 2-trifluoromethy1-4-nitrobenzaldehyde, 5.6 g of cyclohexane-l,3-dione and6.5 g of amidinoacetic acid ethyl ester in 250 ml of ethanol of 2 hours,2-amino-4- (2-trifluoromethyl-4-nitrophenyl )-l ,4,5,6,7,8-hexahydro--oxoquinoline-3-carboxylic acid ethyl ester of melting point264C (ethanol) is obtained. Yield: 62% of theory.

EXAMPLE 37 Heating a solution of 13.2 g of 3-nitrobenzylideneacetoacetic acid ethyl ester and 7.2 g of amidinoaceticacid n-propyl ester in 200 ml of ethanol for 2 hours yields2-amino-6-methyl-4-(3- nitrophenyl l ,4-dihydropyridine-3,5-dicarboxylicacid 3-n-propyl ester S-ethy] ester of melting point 168C (ethanol).

Yield: 79% of theory.

EXAMPLE 38 Boiling a solution of 8.5 g of -nitroveratraldehyde, 4.0 g ofcyclohexane-l ,3-dione and 5.2 g of amidinoacetic acid ethyl ester in150 ml of ethanol for 1 hour yields 2-amino-42-nitro-4.S-dimethoxyphenyl 1,4,5,6,7,8-hexahydro-5-oxoquinoline-3-carboxylic acid ethyl ester ofmelting point 261C (ethanol). Yield: 52% of theory.

EXAMPLE 39 Boiling a solution of 13.2 g of 3-nitrobenzylideneacetoacetic acid ethyl ester and 8.0 g of amidinoaceticacid B-methoxyethyl ester in 200 ml of ethanol for 2 hours yields2-amino-6-methyl-4-(3- nitrophenyl l ,4-dihydropyridine-3,5-dicarboxylic acid 3-(B-methoxyethyl) ester S-ethyl ester of meltingpoint 174C.

Yield: 59% of theory.

EXAMPLE 40 Upon heating a solution of 6.1 g of biphenyl-Z- aldehyde, 3.8g of cyclohexane-l,3-dione and 5.1 g of amidinoacetic acid ethyl esterin ml of ethanol for 1 hour, 2-amino-4-( biphenyl-Z-yl l ,4,5,6,7,8-hexahydro-5-oxoquinoline-3-carboxylic acid ethyl ester of melting point248C (ethanol) is obtained. Yield: 45% of theory.

EXAMPLE 4l Boiling a solution of 13.4 g of( l-naphthylidene) acetoaceticacid ethyl ester and 6.5 g of amidinoacetic acid ethyl ester in 100 mlof ethanol for 8 hours yields 2- amino-6-methyl-4-( l-naphthyl l,4'dihydropyridine- 3,5-dicarboxylic acid diethyl ester of melting point174C (ethanol).

Yield: 62% of theory.

EXAMPLE 42 Upon heating a solution of l 1.5 g of 2-cyanobenzylideneacetoacetic acid methyl ester and 7.2 g of amidinoaceticacid isopropyl ester in 100 m1 of ethanol for 6 hours,2-amino-6-methy14-( 2- cyanophenyl l ,4-dihydropyridine-3,5-dicarboxylic acid 3-isopropyl ester S-methyl ester of melting point21 1C (ethanol) is obtained.

Yield: 72% of theory.

EXAMPLE 43 Upon boiling a solution of 11.5 g of 2-cyanobenzylideneacetoacetic acid methyl ester and 6.5 g of amidinoaceticacid ethyl ester in 100 ml of ethanol for 8 hours,1-amino-6-methyl-4-(2-cyanopheny1)-1,4-dihydropyridine-3,S-clicarboxylic acid 3-ethyl ester 5- methyl ester ofmelting point 224C (ethanol) is obtained.

Yield: 66% of theory.

EXAMPLE 44 Upon boiling a solution of 14.8 g ofZ-phenylbenzylideneacetoacetic acid ethyl ester and 6.5 g ofamidinoacetic acid ethyl ester in 100 ml of ethanol for 8 hours,2-amino-6-methyl-4-(biphenyl-Z-yl l ,4- dihydropyridine-3,S-dicarboxylicacid ethyl ester of melting point 182C (ethanol) is obtained.

Yield: 41% of theory.

EXAMPLE 45 Upon heating a solution of 12.5 g of 3-nitrobenzylideneacetoacetic acid methyl ester and 7.2 g of amidinoaceticacid n-propyl ester in 100 ml of ethanol for 6 hours,2-amino-6-methy1-4-( 3nitropheny1)- l,4-dihydropyridine-3,5-dicarboxylicacid 3-npropyl ester S-methyl ester of melting point 155C (ethanol) isobtained. Yield: 69% of theory.

EXAMPLE 46 Upon heating a solution of l2.l g of (2-thenylidene)acetoacetic acid ethyl ester and 6.5 g of amidinoacetic acid ethyl esterin l ml of ethanol for 4 hours, 2- amino-6-methyl-4-(2-thenyl l.4-dihydropyridine-3,5- dicarboxylic acid diethyl ester of melting point170C (ethanol) is obtained.

Yield: 73% of theory.

EXAMPLE 47 Upon heating a solution of 10.9 g of benzylideneacetoaceticacid dimethylamide and 5.0 g of amidinoacetamide in l00 ml of ethanolfor 8 hours, 2- amino-6-methyl-4-phenyl-5-(N,N- dimethylaminocarbonyl l,4-dihydropyridine-3- carboxylic acid amide of melting point 236C(ethanol) is obtained.

Yield: 50% of theory.

EXAMPLE 48 Heating a solution of l0.9 g of benzylideneacetoacetic aciddimethylamide and 6.5 g of amidinoacetic acid ethyl ester in 100 ml ofmethanol for 6 hours yields 2-amino-6-methyl-4-phenyll,4-dihydropyridine-3,5- dicarboxylic acid 3-ethyl ester5-(N,N-dimethylamide) of melting point 230C (alcohol).

Yield: 61% of theory.

EXAMPLE 49 Boiling a solution of l3.2 g of 2-nitrobenzylideneacetoacetic acid ethyl ester and 7.2 g of amidinoaceticacid isopropyl ester in 100 ml of ethanol for 6 hours yields2-amino-6-methyl-4-(2- nitrophenyl l ,4-dihydropyridine-3,S-dicarboxylicacid 3-isopropyl ester S-ethyl ester of melting pont 139C (isopropanol).

Yield: 39% of theory.

EXAMPLE 50 Boiling a solution of 13.2 g of 2-nitrobenzylideneacetoacetic acid ethyl ester and 6.5 g of amidinoaceticacid ethyl ester in 100 ml of ethanol for 6 hours yields2-amino-6-methyl-4-(2-nitrophenyl)- l,4-dihydropyridine-3,5-dicarboxylicacid diethyl ester of melting point 159C (ethanol).

Yield: 52% of theory.

EXAMPLE 51 Upon heating a solution of 12.5 g of 2-nitrobenzylideneacetoacetic acid methyl ester and 7.2 g of amidinoaceticacid isopropyl ester in 100 ml of ethanol for 8 hours,2-amino-6-methyl-4-(2-nitrophenyl)- l,4-dihydropridine-3,5-dicarboxylicacid 3-isopropyl ester S-methyl ester of melting point 203C(isopropanol) is obtained.

Yield: 50% of theory.

EXAMPLE 52 Upon heating a solution of 12.2 g of 2-cyanobenzylideneacetoacetic acid ethyl ester and 7.2 g of amidinoaceticacid npropyl ester in I00 ml of ethanol for 8 hours.2-amino-6-methyl-4-(2-cyanophenyl)- l,4-dihydropyridine-3,5-dicarboxylicacid 3-n-propyl ester S-ethyl ester of melting point [82C (ethanol) isobtained. Yield: 62% of theory.

EXAMPLE 53 Upon heating a solution of l3.9 g of 3-nitrobenzylideneacetoacetic acid isopropyl ester and 7.2 g ofamidinoacetic acid n-propyl ester in 100 ml of ethanol for 6 hours,2-amino-6-methyl-4-(3- nitrophenyl l ,4-dihydropyridine-3,5-dicarboxylic acid 3-n-propyl ester 5-isopropyl ester of melting point199C (isopropanol) is obtained.

Yield: of theory.

EXAMPLE 54 Heating 21 solution of 6.5 g of 3-cyanobenzaldehyde, 5.6 g ofcyclohexane-l ,3-dione and 6.5 g of amidinoacetic acid ethyl ester inI00 ml of ethanol for 6 hours yields 2-amino-4-( 3-cyanophenyl )-l ,4,5,6,7,8- hexahydro-5-oxoquinoline-3-carboxylic acid ethyl ester ofmelting point 262C (ethanol/dimethylformamide).

Yield: 56% of theory.

EXAMPLE 55 Upon heating a solution of 9.3 g of 3- bromobenzaldehyde, 5.6g of cyclohexane-l,3-dione and 6.5 g of amidinoacetic acid ethyl esterin ml of ethanol for 8 hours, 2-amino-4-( 3-bromophenyl)- l,4,5,6,7,8-hexahydro-5-0xoquinoline-3-carboxylic acid ethyl ester ofmelting point 255C (ethanol) is obtained.

Yield: 44% of theory.

EXAMPLE 56 Upon boiling a solution of 9.3 g of 2- bromobenzaldehyde, 5.6g of cyclohexane-l,3-dione and 6.5 g of amidinoacetic acid ethyl esterin 100 ml of ethanol for 6 hours, 2-amino-4-(2-bromophenyl)- l,4,5,6,7,S-hexahydro-5-oxoquinoline-3-carboxylic acid ethyl ester ofmelting point 245C (ethanol) is obtained.

Yield: 46% of theory.

EXAMPLE 57 Upon heating a solution of 8.9 g of 3-carbethoxybenzaldehyde,5.6 g of cyclohexane-l ,3-dione and 6.5 g of amidinoacetic acid ethylester in 100 ml of ethanol for 4 hours, 2-amino-4-( 3-carbethoxyphenyl)-l ,4,5,6,7,8- hexahydro-S-oxoquincline-3-carboxylic acid ethyl esterof melting point 234C (ethanol) is obtained. Yield: 54% of theory.

EXAMPLE 58 vessel dilating amount or an antihypertensive amount of acompound of the formula:

wherein R is phenyl; substituted phenyl in which the substituents areone to three members selected from the group consisting of lower alkyl,lower alkoxy, halogeno, nitro, cyano, trifluoromethyl, azido,carbo(lower alkoxy), lower alkylsulfonyl, lower alkylsulfinyl, loweralkylthio and phenyl, or naphthyl R is hydrogen. lower alkyl or phenyl;

R is lower alkoxy, lower alkoxy(lower alkoxy),

lower alkenyloxy or lower alkynyloxy; and

R is lower alkoxy, lower alkoxy( lower alkoxy),

lower alkenyloxy or lower alkynyloxy in combination with apharmaceutically acceptable nontoxic inert diluent or carrier.

2. A composition according to claim 1 wherein R is phenyl.

3. A composition according to claim 2 wherein R is naphthyl; phenyl;phenyl substituted with from one to three substituents selected from thegroup consisting of lower alkyl, lower alkoxy, halogeno, nitro cyano,trifluoromethyl, azido, carbo(lower alkoxy), lower alkylsulfonyl, loweralkylsulfinyl and lower alkylthio; or biphenyl.

4. A composition according to claim 3 wherein the compound is2-amino-6-methyl-4-phenyl-1 ,4- dihydropyridine-3,S-dicarboxylic aciddiethyl ester.

5. A composition according to claim 3 wherein the compound is2-amino-6-methyl-4-(2-nitrophenyl-l,4- dihydropyridine-3.5-dicarboxylicacid diethyl ester.

6. A composition according to claim 3 wherein the compound is2-amino-6-methyl-4-(Z-methoxyphenyl)-l,4-dihydropyridine-3.S-dicarboxylic acid diethyl ester.

7. A composition according to claim 3 wherein the compound is2-amino-6-methyl-4-(2-cyanophenyl)- l,4-dihydropyridine-3,S-dicarboxylicacid diethyl ester.

8. A composition according to claim 3 wherein the compound is2-amino-6-methyl-4-( 2- trifluoromethylphenyl l ,4-dihydropridine-3,5-dicarboxylic acid diethyl ester.

9. A composition according to claim 3 wherein the compound is2-amino-6-methyl-4-( 3-nitrophenyl) 1,4-dihydropyridine-3,5-dicarboxylic acid diethyl ester.

10. A composition according to claim 3 wherein the compound is2-amino-6-methyl-4-(3-nitrophenyl)-l ,4-dihydropyridine-3,S-dicarboxylic acid 3-ethyl ester-5- methyl ester.

1 l. A composition according to claim 3 wherein the compound is2-amino-6-methyl-4-( 3-nitrophenyl)-l,4-dihydropyridine-3,5-dicarboxylic acid 3-ethyl ester-5- (fi-methoxyethyl)ester.

12. A composition according to claim 1 in oral administration form.

13. A composition according to claim 1 in parenteral administrationform.

14. A composition according to claim 1 wherein the compound is2-amino-6-methyl-4-(2-nitrophenyl )-l ,4-dihydropyridine-3,5-dicarboxylic acid 3-ethyl ester 5- methyl ester.

15. A composition according to claim 1 wherein the compound is2-amino-6-methyl-4-(2-methylphenyl)-1,4-dihydropyridine-3,5-dicarboxylic acid diethyl ester.

16. A composition according to claim 1 wherein the compound is2-amino-6-methyl-4-(3-chlorophenyl)-1,4-dihydropyridine-3,5-dicarboxylic acid diethyl ester.

17. A composition according to claim 1 wherein the compound is2-amino-6-methyl-4-(4- methylmercaptophenyl)- l ,4-dihydropyridine-3,5-dicarboxylic acid diethyl ester.

18. A composition according to claim 1 wherein the compound is2-amino-6-methyl-4-(3-nitrophenyl)-1,4- dihydropyridine-3,S-dicarboxylicacid 3-ethyl 5- isopropyl ester.

19. A composition according to claim 1 wherein the compound is2-amino-6-methyl-4-(3-nitrophenyl)-1,4- dihydropyridine-3,5-dicarboxylicacid 3-ethyl ester 5- propargyl ester.

20. A composition according to claim 1 wherein the compound is2-amino-6-methyl-4-( 3-nitro-6- chlorophenyl )-l ,4-dihydropyridine-3,S-dicarboxyl ic acid S-ethyl ester S-methyl ester.

21. A composition according to claim 1 wherein the compound is2-amino-6-methyl-4-(fur-2-yl l ,4- dihydropyridine-3,5-dicarboxylic aciddiethyl ester.

22. A composition according to claim 1 wherein the compound is2-amino-4,6-diphenyll ,4- dihydropyridine-3,5-dicarboxylic acid ethylester.

23. A composition according to claim 1 wherein the compound is2-amino-4,6-dimethyl-l ,4- dihydropyridine-3,5-dicarboxylic acid dietherester.

24. A composition according to claim 1 wherein the compound is2-amino-4-methyl-l ,4,5,6,7,8-hexahydro- 5-oxoquinoline-3'carboxylicacid ethyl ester.

25. A composition according to claim 1 wherein the compound is2-amino-4-(3-chlorophenyl)-l,4,5,6,7,8-hexahydro-S-oxoquinoline-3-carboxylic acid ethyl ester.

26. A composition according to claim 1 wherein the compound is2-amino-4-(a-pyridyl)- l ,4,5,6,7,8-hexahydro-S-oxoquinoline-B-carboxylic acid ethyl ester.

27. A composition according to claim 1 wherein the compound is2-amino-4-(quinol-4-yl)-l,4,5,6,7,8- hexahydro-S-oxoquinoline-carboxylicacid 3-ethyl ester.

28. A composition according to claim 1 wherein the compound is2-amino-4-(4,6-dimethoxypyrimid-5-yl)- l,4,5,6,7,S-hexahydro-5-oxoquinoline-3-carboxylic acid ethyl ester.

29. A composition according to claim 1 wherein the compound is2-amino-4-(naphth-l-yl)-l,4,5,6,7.8-hexahydro-S-oxoquinoline-3-carboxylic acid ethyl ester.

30. A composition according to claim 1 wherein the compound is2-amino-4-(isoquinol-l-yl l ,4,5,6,7,8-

hexahydro-S-oxoquinolinel3-carboxylic acid ethyl ester.

31. A composition according to claim 1 wherein the compound is2-amino-4-( fi-methylpyrid-Z-yl1,4,5,6,7,8-hexahydro--oxoquinoline-3-carboxylic acid ethyl ester.

32. A composition according to claim 1 wherein the compound is2-amino-6-methyl-5-carbethoxy-4-(3- nitrophenyl )-l,4-dihydropyridine-3-carboxylic acid amide.

33. A composition according to claim 1 wherein the compound is2-amino-4-(2-cyanophenyl)-l,4,5,6,7,8-hexahydro-S-oxoquinoline-3-carboxylic acid ethyl ester.

34. A composition according to claim I wherein the compound is2-amino-6-methyl-4-(3-nitrophenyl)-1,4- dihydropyridine-3,S-dicarboxylicacid 3-isopropyl ester S-ethyl ester.

35. A composition according to claim 1 wherein the compound is2-amino-6-methyl-4-( 2- trifluoromethylphenyl l ,4-dihydropyridine-3,5-dicarboxylic acid 3-isopropyl ester S-ethyl ester.

36. A composition according to claim 1 wherein the compound is2-amino-6-methyl-4-(3-nitrophenyl)-l,4- dihydropyridine-3,S-dicarboxylicacid diisopropyl ester.

37. A composition according to claim 1 wherein the compound is2-amino-6-methyl-4-(2-cyanophenyl)- l,4-dihydropyridine-3,5-dicarboxylicacid 3-isopropyl ester Sethyl ester.

38. A composition according to claim 1 wherein the compound is2-amino-6-methyl-4-( 3-nitrophenyl)-l ,4-dihydropyridine-3.5dicarboxylic acid 3-isopropyl ester S-methyl ester.

39. A composition according to claim 1 wherein the compound is2-amino-4-( 2-trifluoromethyl4- nitrophenyl )-l ,4,5,6,7,8-hexahydro-5-oxoquinoline- 3 carboxylic acid ethyl ester.

40. A composition according to claim 1 wherein the compound is2-amino-6-methyl-4-(3-nitrophenyl)-l ,4-dihydropyridine-3.5-dicarboxylic acid 3-n-propyl ester S-ethyl ester.

41. A composition according to claim 1 wherein the compound is2-amino-4-(2nitro4,5- dimethoxyphenyl l ,4,5,6,7,8-hexahydro5-oxoquinoline-3-carboxylic acid ethyl ester.

42. A composition according to claim 1 wherein the compound is2-amino-6-methyl-4-( 3-nitrophenyl 1,4- dihydropyridine-3,S-dicarboxylicacid 3-(13- methoxyethyl) ester S-ethyl ester.

43. A composition according to claim 1 wherein the compound is2-amino-4-(biphenyl-2-yl)l,4,5,6,7,8-hexahydro-S-oxoquinoline-3-carboxylic acid ethyl ester.

44. A composition according to claim 1 wherein the compound is2-amino-6-methyl-4-( l-naphthyl )-l ,4- dihydropyridine-3,S-dicarboxylicacid diethyl ester.

45. A composition according to claim 1 wherein the compound is2-amino-6-methyl-4-(2-cyanophenyl)- l,4-dihydropyridine-3,S-dicarboxylicacid 3-isopropyl ester S-methyl ester.

46. A composition according to claim 1 wherein the compound is2-amino-6-methyl-4-(2-cyanophenyl) l.4-dihydropyridine-3.S-dicarboxylicacid 3-ethyl ester S-methyl ester.

47. A composition according to claim 1 wherein the compound is2-amino-6-methyl-4-( biphenyl-2-yl )-l ,4-dihydropyridine-3,5-dicarboxylic acid ethyl ester.

48. A composition according to claim 1 wherein the compound is 2-amino-6methyl-4-(3-nitrophenyl)-l,4- dihydropyridine-35-dicarboxylic acid3-n-propyl ester S-methyl ester.

49. A composition according to claim 1 wherein the compound is2-amino-6-methyl-4-(Z-thenyl)-1,4- dihydropyridine-3,S-dicarboxylic aciddiethyl ester.

50. A composition according to claim 1 wherein the compound is2-amino-6-methyl-4-phenyl-5-(N,N-dimethylaminocarbonyl)-1,4-dihydropyridine-3- carboxylic acid amide.

51. A composition according to claim 1 wherein the compound is2-amino-6-methyl-4-phenyll ,4- dihydropyridine-3,5-dicarboxylic acid3-ethyl ester 5- (N,N-dimethylamide 52. A composition according to claim1 wherein the compound is 2-amino-6-methyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylic acid 3-isopropyl ester S-ethyl ester.

53. A composition according to claim 1 wherein the compound is2-amidino-6-methyl-4-(2-nitrophenyll,4-dihydropyridine-3,S-dicarboxylicacid 3-isopropyl ester S-methyl ester.

54. A composition according to claim 1 wherein the compound is2-amino-6-methyl-4-(2-cyanophenyl)- l,4-dihydropyridine-3,S-dicarboxylicacid 3-n-propyl ester S-ethyl ester.

55. A composition according to claim 1 wherein the compound is2-amino-6-methyl-4(3-nitrophenyl)-1,4- dihydropyridine-3,S-dicarboxylicacid 3-n-propyl ester S-isopropyl ester.

56. A composition according to claim 1 wherein the compound is2-amino-4-(3-cyanophenyl)-l,4,5,6,7,8-hexahydro-S-oxoquinoline-3-carboxylic acid ethyl ester.

57. A composition according to claim 1 wherein the compound is2-amino-4-(3-bromophenyl )-l ,4,5,6,7,8-hexahydro-S-oxoquinoline-3-carboxyiic acid ethyl ester.

58. A composition according to claim 1 wherein the compound is2-amino-4-(2-bromphenyl)-l,4,5,6,7,8-hexahydro-S-oxoquinoline-3-carboxylic acid ethyl ester.

59. A composition according to claim 1 wherein the compound is2-amino-4-( 3-carbethoxyphenyl,4,5,6,7,8-hexahydro-5-oxoquinoline-3-carboxylic acid ethyl ester.

60. A composition to claim 1 wherein the compound is 2-amino-4(2-azidophenyl)-l ,4.5,6,7,8-hexahydro-5- oxoquinoline-3-carboxylic acidethyl ester.

61. A method of effecting coronary vessel dilation in humans and animalswhich comprises administering to such human or animal in need thereof acoronary vessel dilating amount of a compound of the formula:

wherein R is phenyl; substituted phenyl in which the substituents areone to three members selected from the group consisting of lower alkyl,lower alkoxy, halogeno, nitro, cyano, trifluoromethyl, azido,carbo(1ower alkoxy), lower alkylsulfonyl, lower alkylsulfinyl, loweralkylthio and phenyl; or napthyl R is hydrogen, lower alkyl or phenyl;

R is lower alkoxy, lower alkoxy(lower alkoxy),

lower alkenyloxy or lower alkynyloxy;

and

R is lower alkoxy, lower alkoxy(lower alkoxy),

lower alkenyloxy or lower alkynyloxy.

62. A method according to claim 61 wherein R is phenyl.

63. A method according to claim 62 wherein R is naphthyl; phenyl; phenylsubstituted with from one to three substituents selected from the groupconsisting of lower alkyl, lower alkoxy, halogeno, nitro, cyano,trifluoromethyl, azido, carbo(lower alkoxy), lower alkylsulfonyl, loweralkylsulfinyl and lower alkylthio; or biphenyl.

64. A method according to claim 63 wherein the compound is2-amino-6-methyl-4-phenyll ,4- dihydropyridine-3.S-dicarboxylic aciddiethyl ester.

65. A method according to claim 63 wherein the compound is2-amino-6-methyl-4-( 2-nitrophenyl l ,4-dihydropyridine-3,S-dicarboxylic acid diethyl ester.

66. A method according to claim 63 wherein the compound is2-amino-6-methyl-4-( 2-methoxyphcnyll,4-dihydropyridine-3,S-dicarboxylic acid diethyl ester.

67. A method according to claim 63 wherein the compound is2-amino-6-methyl-4-(2-cyanophenyl)- l,4-dihydropyridine-3,5-dicarboxylicacid diethyl ester.

68. A method according to claim 63 wherein the compound is2-amino-6-methyl-4-( 2- trifluoromethylphenyl 1 ,4-dihydropyridine-3,5dicarhoxylic acid diethyl ester.

69. A method according to claim 63 wherein the compound is2-amino-6-methyl-4-( 3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylic acid diethyl ester.

70. A method according to claim 63 wherein the compound is2-amino-6-methyl-4-( 3-nitrophenyl)-l,4-dihydropyridine-3,S-dicarboxylic acid 3-ethyl ester-5- methyl ester.

71. A method according to claim 63 wherein the compound is2-amino-6-methyl-4-( 3-nitrophenyl)-l,4-dihydropyridine-3,S-dicarboxylic acid 3-ethyl ester-5- (B-methoxyethyl)ester.

72. A method according to claim 61 wherein the compound is2-amino-6-methyl-4-( 2-nitrophenyl)-l ,4-dihydropyridine-3,S-dicarboxylic acid 3-ethyl ester 5- methyl ester.

73. A method according to claim 61 wherein the compound is2-amino-6-methyl-4-(2-methylphenyl)-l,4-dihydropyridine-3,S-dicarboxylic acid diethyl ester.

74. A method according to claim 61 wherein the compound is2-amino-6-methyl-4-(3-chlorophenyl)-l,4-dihydropyridine-3,5-dicarboxylic acid diethyl ester.

75. A method according to claim 61 wherein the compound is2-amino-6-methyl-4-( 4- methylmercaptophenyl l ,4-dihydropyridine-3,5-dicarboxylic acid diethyl ester.

76. A method according to claim 61 wherein the compound is2-amino-6-methyl-4-( 3-nitrophenyl l .4-dihydropyridine-3,S-dicarboxylic acid 3-ethyl S- isopropyl ester.

77. A method according to claim 61 wherein the compound is2-amino-6-methyl-4-(3-nitrophenyl)-l,4- dihydropyridine-3,S-dicarboxylicacid 3-ethyl ester 5- propargyl ester.

78. A method according to claim 61 wherein the compound is2-amino-6-methyl-4-( 3-nitro-6- chlorophenyl )-1 ,4-dihydropyridine-3,S-dicarboxylic acid 3-ethyl ester S-methyl ester.

79. A method according to claim 61 wherein the compound is2-amino-6-methyl-4-(fur-2-yl l ,4- dihydropyridine-3,5-dicarboxylic aciddiethyl ester.

80. A method according to claim 61 wherein the compound is2-amino-4,6-diphenyl- 1 ,4- dihydropyridine-3.S-dicarboxylic acid ethylester.

81. A method according to claim 61 wherein the compound is2-amino-4,6-dimethyl- 1 ,4- dihydropyridine-3,S-dicarboxylic aciddiethyl ester.

82. A method according to claim 61 wherein the compound is2-amino-4-methyl-l ,4,5,6,7,8-hexahydro- 5-oxoquinoline-3-carboxylicacid ethyl ester.

83. A method according to claim 61 wherein the compound is 2-amino-4-(3-chlorophenyl l ,4,5 67,8- hexahydro-S-oxoquinoline-3-carboxylic acidethyl ester.

84. A method according to claim 61 wherein the compound is2-amino-4-(a-pyridyl)- l ,4,5,6,7,8-hexahydro-S-oxoquinoline-3-carboxylic acid ethyl ester.

85. A method according to claim 61 wherein the compound is2-amino-4-(quinol-4-yl l ,4.5.6,7,8- hexahydro-S-oxoquinoline-carboxylicacid 3-ethyl ester.

86. A method according to claim 61 wherein the compound is2-amino-4-(4,6-dimethoxypyrimid-5-yl)-l,4,5,6,7,S-hexahydro-S-oxoquinoline-3-carboxylic acid ethyl ester.

87. A method according to claim 61 wherein the compound is2-amino-4-(naphth-l-yl)-l,4,S,6,7,8-hexahydro-S-oxoquinoline-3-carboxylic acid ethyl ester.

88. A method according to claim 61 wherein the compound is2-amino-4-(isoquinoll -y] )-l ,4,5,6,7,8-hexahydro5-oxoquinoline-3-carboxylic acid ethyl ester.

89. A method according to claim 61 wherein the compound is2-amino-4-(6-methylpyrid-2-yl)-l,4,5,6,7,8-hexahydro-S-oxoquinoline-3-carboxylic acid ethyl ester.

90. A method according to claim 61 wherein the compound is2-amino-6-methyl-5-carbethoxy-4-(3- nitrophenyl l,4-dihydropyridine-3-carboxylic acid amide.

91. A method according to claim 61 wherein the compound is 2-amino-4-(2-cyanophenyl l ,4,5,6,7,8- hexahydro-S-oxoquinoline-3-carboxylic acidethyl ester.

92. A method according to claim 61 wherein the compound is2-amino-6-methyl-4-(3-nitrophenyl))-l,4-dihydropyridine-3,S-dicarboxylic acid 3-isopropyl ester S-ethylester.

93. A method according to claim 61 wherein the compound is2-amino-6-methyl-4-( 2- compound is 2-amino-6-methyl-4-(3-nitrophenyl)-l ,4- q

dihydropyridine-3,5-dicarboxylic acid 3-n-propyl ester S-ethyl ester.

99. A method according to claim 61 wherein the compound is2-amino-4-(2-nitro-4,5- dimethoxyphenyl l .4,5,6,7,8-hexahydro-5oxoquinoline-3-carboxylic acid ethyl ester.

100. A method according to claim 61 wherein the compound is2-amino-6-methyl-4-( 3-nitrophenyl)-l,4-dihydropyridine-3,S-dicarboxylic acid 3-( B- methoxyethyl) ester 5 ethylester.

101. A method according to claim 61 wherein the compound is2-amino-4-(biphenyl-2-yl)-l,4,5,6,7,8-hexahydro-S-oxoquinoline-3-carboxylic acid ethyl ester.

102. A method according to claim 61 wherein the compound is2-amino-6-methyl-4-( l-naphthyl)-l,4- dihydropyridine-3,S-dicarboxylicacid diethyl esterv 103. A method according to claim 61 wherein thecompound is 2-amino-6-methyl-4-(2-cyanophenyl)-l,4-dihydropyridine-3,S-dicarboxylic acid 3-isopropyl ester S-methylester.

104. A method according to claim 61 wherein the compound is2-amino-6-methyl-4-(2-cyanophenyl)- l 4-dihydropyridine-3,S-dicarboxylicacid 3-ethyl ester S-methyl ester.

105. A method according to claim 61 wherein the compound is2-amino-6methyl-4-(biphenyl-2-yl l ,4- dihydropyridine-3.S-dicarboxylicacid ethyl ester.

106. A method according to claim 61 wherein the compound is2-amino-6-methyl-4-(3-nitrophenyl)-l,4- dihydropyridine-3,5-dicarbxylicacid 3-n-propyl ester S-methyl ester.

107. A method according to claim 61 wherein the compound is2-amino-6-methyl-4-( Z-thenyl l ,4- dihydropyridine-3,5-dicarboxylicacid diethyl ester.

108. A method according to claim 61 wherein the compound isZ-amino-6-methyl-4-phenyl-5-(N,N- dimethylaminocarbonyl l,4-dihydropyridine-3- carboxylic acid amide.

109. A method according to claim 61 wherein the compound is2-amino-6-methyl-4-phenyl-l ,4- dihydropyridinc-3,5-dicarboxylic acid3-ethyl ester NN-dimethylamide).

110. A method according to claim 61 wherein the compound is2-amino-6-methyl-4(Z-nitrophenyl l ,4- dihydropyridine-3,5-dicarboxylicacid acid 3-isopropyl ester 5-ethyl ester.

111. A method according to claim 61 wherein the compound is2-amidino-6-methyl-4-(2-nitrophenyl)-l,4-dihydropyridine-3,5-dicarboxylic acid 3-isopropyl ester S-methylester.

112. A method according to claim 61 wherein the compound is2-amino-6-methyl-4-(Z-cyanophenyl)- l,4-dihydropyridine-3,5dicarboxylicacid 3-n-propyl ester S-ethyl ester.

113. A method according to claim 61 wherein the compound is2-amino-6-methyl-4-( 3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylic acid 3-n-propyl ester 5-isopropylester.

114. A method according to claim 61 wherein the compound is2-arnino-4-(3-cyanophenyl)-1,4,5,6,7,8- hexahydro-S-oxoquinoline3-carboxylic acid ethyl ester.

115. A method according to claim 61 wherein the compound is 2-amino-4-(3-bromophenyl)-l,4,5,6,7,8- hexahydro-5-oxoquinoline-3-carboxylic acidethyl ester.

116. A method according to claim 61 wherein the compound is 2-amino-4-(2-bromophenyl)-l,4,5,6,7,8- hexahydro-5-oxoquinoline-3-carboxylic acidethyl ester.

117. A method according to claim 61 wherein the compound is 2-amino-4-(3-carbethoxyphenyl)- l 4,5,6,7,8-hexahydro-5-oxoquinoline-3-carboxylicacid ethyl ester.

118. A method according to claim 61 wherein the compound is 2-amino-4-(2-azidophenyl )-l ,4,5,6,7,8- hexahydro-S-oxoquinoline-B-carboxylic acidethyl ester.

119. A method of treating hypertension in humans and animals whichcomprises administering to such human or animal in need thereof anantihypertensive amount of a compound of the formula:

0 H ll 121. A method according to claim 120 wherein R is naphthyl;phenyl; phenyl substituted with from one to three substituents selectedfrom the group consisting of lower alkyl, lower alkoxy, halogeno, nitro,cyano. trifluoromethyl, azido, carbo(lower alkoxy), lower alkylsulfonyl,lower alkylsulfinyl and lower alkylthio; or biphenyl.

122. A method according to claim 121 wherein the compound is2-amino-6-methyl-4-phenyll ,4- dihydropyridine-3,S-dicarboxylic aciddiethyl ester.

123. A method according to claim 121 wherein the compound is2-amino-6-methyl-4-(2-nitrophenyl)-1,4- dihydropyridine-3,S-dicarboxylicacid diethyl ester.

124. A method according to claim 121 wherein the compound is2-amino-6-methyl-4-( 2-methoxyphenyl)-l,4-dihydropyridine-3,S-dicarboxylic acid diethyl ester.

125. A method according to claim 121 wherein the compound is2-amino-6-methyl-4-(2-cyanophenyl)- 1,4-dihydropyridine-3,S-dicarboxylicacid diethyl ester.

126. A method according to claim 121 wherein the compound is2-amino-6-methyl-4-( 2- trifluoromethylphenyl l ,4-dihydropyridine-3,5-dicarboxylic acid diethyl ester.

127. A method according to claim 121 wherein the compound is2-amino-6-methyl-4-( 3-nitrophenyl)l,4- dihydropyridine-3,S-dicarboxylicacid diethyl ester.

128. A method according to claim 12] wherein the compound is2amino-6-methyl-4-( 3-nitrophenyl)-l,4- dihydropyridine-3,S-dicarboxylicacid 3-ethyl ester-5- methyl ester.

129. A method according to claim 12] wherein the compound is2-amino-6-methyl-4-( 3-nitrophenyl)-l ,4-dihydropyridine-3,S-dicarboxylic acid 3-ethyl ester-5- (B-rnethoxyethyl)ester.

130. A method according to claim 119 wherein the compound is2-amino-6-methyl-4-( 2-nitrophenyl)-l ,4-dihydropyridine-3,5-dicarboxylic acid 3-ethyl ester 5- methyl ester.

131. A method according to claim 119 wherein the compound is2-amino-6-methyl-4-(2-methylphenyl)-l,4-dihydropyridine-3.S-dicarboxylic acid diethyl ester.

132. A method according to claim 119 wherein the compound is2-amino-6-methyl-4-(3-chlorophenyl)-l.4-dihydropyridine-3,5-dicarboxylic acid diethyl ester.

133. A method according to claim 119 wherein the compound is2-amino-6-methyl-4-( 4- methylmercaptophenyl 1 ,4-dihydropyridine-3,5-dicarboxylic acid diethyl ester.

134. A method according to claim 119 wherein the compound is2-amino-6-methyl-4-( 3-nitrophenyl)-1,4-dihydropyridine-3,S-dicarboxylic acid 3-ethyl 5- isopropyl ester.

135. A method according to claim 119 wherein the compound is2-amino-6-methyl-4-(3-nitrophenyl)-1 ,4-dihydropyridine-3,5-dicarboxylic acid 3-ethyl ester 5- propargyl ester.

136. A method according to claim 119 wherein the compound is2-amino-6-methyl-4-( 3-nitro-6- chlorophenyl)-1.4-dihydropyridine-3,S-dicarboxylic acid 3-ethyl ester S-methyl ester.

137. A method according to claim 119 wherein the compound is2-amino-6-methyl-4-(fur-2-yl )-1 ,4- didhydropyridine-B,S-dicarboxylicacid diethyl ester.

138. A method according to claim 119 wherein the compound is2-amino-4,6-diphenyll ,4- dihydropyridine-3,S-dicarboxylic acid ethylester.

139. A method according to claim 119 wherein the compound is2-amino-4,6-dimethyll ,4- dihydropyridine-3,5-dicarboxylic acid diethylester.

140. A method according to claim 119 wherein the compound is2-amino-4-methyll ,4,5,6,7,8-hexahydro- 5-oxoquinoline-3-carboxylic acidethyl ester.

14]. A method according to claim 119 wherein the compound is2-amino-4-(3-chlorophenyl)-l ,4,5,6,7,8-hexahydro-S-oxoquinoline-3-carboxylic acid ethyl ester.

142. A method according to claim 119 wherein the compound is2-amino-4-(a-pyridyU-1,4,5,6,7,8- hexahydro-S-oxoquinoline-3-carboxylicacid ethyl ester.

143. A method according to claim 119 wherein the compound is2-21mino-4-(quinol-4-yl )-1 ,4,5,6,7,8-hexahydro-S-oxoquinoline-carboxylic acid B-ethyl ester.

144. A method according to claim 119 wherein the compound is2-amino-4-(4,6-dimethoxypyrimid-5-yl)- 1,4,5,6,7,8-hexahydro-5-oxoquinoline-3-carboxylic acid ethyl ester.

145. A method according to claim 119 wherein the compound is 2-amino-4-(naphthl -yl l ,4,5,6,7,8- hexahydro-5-oxoquinoline-3-carboxylic acidethyl ester.

146. A method according to claim 119 wherein the compound is2-amino-4-(isoquinoll -yl)- l .4,5,6,7,8-hexahydro-S-oxoquinoline-3-carboxylic acid ethyl ester.

147. A method according to claim 119 wherein the compound is2-amino-4-(6-methylpyrid-2-yl)-l,4,5,6,7,8-hexahydro-5-oxoquinoline-3-carboxylic acid ethyl ester.

148. A method according to claim 119 wherein the compound is2-amino-6-methyl-5-carbethoxy-4-( 3- nitrophenyl l,4-dihydropyridine-3-carboxy1ic acid amide.

149. A method according to claim 119 wherein the compound is2-amino-4-(2-cyanophenyl l ,4,5,6,7,8-hexahydro-S-oxoquinoline-3-carboxylic acid ethyl ester.

150. A method according to claim 119 wherein the compound is2-amino-6-methyl-4-( 3-nitrophenyl)-l,4-dihydropyridine-3,5-dicarboxylic acid 3-isopropyl ester S-ethyl ester.

151. A method according to claim 119 wherein the compound is2-amino-6-methyl-4-( 2- trifluoromethylphenyl 1 ,4-dihydr0pyridine-3 ,5-dicarboxylic acid 3-isopropyl ester S-ethyl ester.

152. A method according to claim 119 wherein the compound is2-amino-6-methyl-4-(3-nitrophenyl)-l,4- dihydropyridine-3,5-dicarboxylicacid diisopropyl ester.

153. A method according to claim 119 wherein the compound is2-amino-6-methyl-4-(Z-cyanophenyl)- 1,4-dihydropyridine-3,S-dicarboxylicacid 3-isopropyl ester S-ethyl ester.

154. A method according to claim 119 wherein the compound is2-amino-6-methyl-4-(3-nitrophenyl 1,4- dihydropyricline-3,5-dicarboxylicacid 3-isopropyl ester S-methyl ester.

155. A method according to claim 119 wherein the compound is 2-amino-4-(2-trifl uoromethyl-4- 27nitrophenyl)-1.4,S,6.7.8-hexahydro--oxoquinoline-3- carboxylic acidethyl ester.

156. A method according to claim 119 wherein the compound is2-amino-6-methyl-4-( 3-nitrophenyl)-l ,4-dihydropyridine-3,5-dicarboxylic acid 3-n-propyl ester S-ethyl ester.

157. A method according to claim 119 wherein the compound is 2-amino-4-(2-nitro-4,5- dimethoxyphenyl )-l ,4,5,6,7,8-hexahydr0-5-oxoquinoline-la-carboxylic acid ethyl ester.

158. A method according to claim 119 wherein the compound is2-amino-6-methyI-4-(3-nitrophenyl)-l ,4-dihydropyridine-3,S-dicarboxylic acid 3-( B- methoxyethyl) ester S-ethylester.

159. A method according to claim [19 wherein the compound is 2-amino-4-(biphenyl-Z-yl )-l ,4,5,6,7,8- hexahydro-S-oxoquinoline-3-carboxylic acidethyl ester.

160. A method according to claim 119 wherein the compound is2-amino-6-methyl-4-( l-naphthylJ-l ,4- dihydropyridine-3,S-dicarboxylicacid diethyl ester.

161. A method according to claim 119 wherein the compound is2-amino-6-methyl-4-(2-cyanophenyl)- l,4-dihydropyridine-3,5-dicarboxylicacid 3-isopropyl ester S-methyl ester.

162. A method according to claim 119 wherein the compound is2-amino-6-methyl-4-(2-cyanophenyl)- l,4-dihydropyridine-3,S-dicarboxylicacid 3-ethyl ester S-methyl ester.

163. A method according to claim 119 wherein the compound is2-amino-6-methyl-4-(biphenyl-2-yl)-l ,4-dihydropyridine-3,S-dicarboxylic acid ethyl ester.

164. A method according to claim 119 wherein the compound is2-amino-6-methyl-4-(3-nitrophenyl)-1,4- dihydropyridine-3,5-dicarboxylicacid 3-n-propyl ester S-methyl ester.

165. A method according to claim 119 wherein the compound is2-amino-6-methyl-4-( Z-thenyl l ,4- dihydropyridine-3,5-dicarboxylicacid diethyl ester.

166. A method according to claim 119 wherein the compound is2-amino-6-methyl-4-phenyl-5-(N,N- dimethylaminocarbonyl,4-dihydropyridine-3- carboxylic acid amide.

167. A method according to claim 119 wherein the compound is2-amino-6-methyl-4-phenyll ,4- dihydropyridine-3.S-dicarboxylic acid3-ethyl ester (5- N.N-dimethylamidc).

168. A method according to claim 119 wherein the compound is2-amino-6-methyl-4-(Z-nitrophenyl l ,4- dihydropyridine-3,5-dicarboxylicacid acid 3-isopropyl ester S-ethyl ester.

169. A method according to claim 119 wherein the compound is2-amidino-6-methyl-4-(Z-nitrophenyl)-l,4-dihydropyridine-3,S-dicarboxylic acid 3-isopropyl ester S-methylester.

170. A method according to claim 119 wherein the compound is2-amino-6-methyl-4-(2-cyanophenyl)- l,4-dihydropyridine-3,S-dicarboxylicacid 3-n-propyl ester 5-ethyl ester.

171. A method according to claim 119 wherein the compound is2-amino-6-methyl-4-(3-nitrophenyl)-l,4- dihydropyridine-3,5-dicarboxylicacid 3-n-propyl ester S-isopropyl ester.

172. A method according to claim 119 wherein the compound is2-amino-4-(3-cyanophenyl)-l,4,5,6,7,8- hexahydro-S-oxoquinoline3-carboxylic acid ethyl ester.

173. A method according to claim 119 wherein the compound is 2-amino-4-(3-bromophenyl l ,4,5,6,7,8- hexahydro-S-oxoquinoline-3-carboxylic acidethyl ester.

174. A method according to claim 119 wherein the compound is2-amino-4-(2-bromophenyl)-l,4,5,6,7,8-hexahydro-S-oxoquinoline-3-carboxylic acid ethyl ester.

175. A method according to claim 119 wherein the compound is 2-amino-4-(3-carbethoxyphenyl l,4.5,6,7,8-hexahydro-5-oxoquinoline-3-carboxylicacid ethyl ester.

176. A method according to claim 119 wherein the compound is2-amino-4-(2-azidophenyl)-1,4,5,6,7,8-hexahydro-5-oxoquinoline-3-carboxylic acid ethyl ester.

1. A PHARMACEUTICAL COMPOSITION USEFUL FOR EFFECTING CORONARY VESSELDIALTION AND FOR TREATING HYPERTENSION IN HUMANS AND AMIMALS WHICHCOMPRISES A CORONARY VESSEL DILATING AMOUNT OR AN ANTIHYPERTENSIVEAMOUNT OF A COMPOUND OF THE FORMULA:
 2. A composition according to claim1 wherein R1 is phenyl.
 3. A composition according to claim 2 wherein Ris naphthyl; phenyl; phenyl substituted with from one to threesubstituents selected from the group consisting of lower alkyl, loweralkoxy, halogeno, nitro cyano, trifluoromethyl, azido, carbo(loweralkoxy), lower alkylsulfonyl, lower alkylsulfinyl and lower alkylthio;or biphenyl.
 4. A composition according to claim 3 wherein the compoundis 2-amino-6-methyl-4-phenyl-1,4-dihydropyridine-3,5-dicarboxylic aciddiethyl ester.
 5. A composition according to claim 3 wherein thecompound is2-amino-6-methyl-4-(2-nitrophenyl-1,4-dihydropyridine-3,5-dicarboxylicacid diethyl ester.
 6. A composition according to claim 3 wherein thecompound is2-amino-6-methyl-4-(2-methoxyphenyl)-1,4-dihydropyridine-3,5-dicarboxylicacid diethyl ester.
 7. A composition according to claim 3 wherein thecompound is2-amino-6-methyl-4-(2-cyanophenyl)-1,4-dihydropyridine-3,5-dicarboxylicacid diethyl ester.
 8. A composition according to claim 3 wherein thecompound is2-amino-6-methyl-4-(2-trifluoromethylphenyl)-1,4-dihydropridine-3,5-dicarboxylic acid diethyl ester.
 9. A composition according to claim 3wherein the compound is2-amino-6-methyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylicacid diethyl ester.
 10. A composition according to claim 3 wherein thecompound is2-amino-6-methyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylicacid 3-ethyl ester-5-methyl ester.
 11. A composition according to claim3 wherein the compound is2-amino-6-methyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylicacid 3-ethyl ester-5-( Beta -methoxyethyl) ester.
 12. A compositionaccording to claim 1 in oral administration form.
 13. A compositionaccording to claim 1 in parenteral administration form.
 14. Acomposition according to claim 1 wherein the compound is2-amino-6-methyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylicacid 3-ethyl ester 5-methyl ester.
 15. A composition according to claim1 wherein the compound is2-amino-6-methyl-4-(2-methylphenyl)-1,4-dihydropyridine-3,5-dicarboxylicacid diethyl ester.
 16. A composition according to claim 1 wherein thecompound is2-amino-6-methyl-4-(3-chlorophenyl)-1,4-dihydropyridine-3,5-dicarboxylicacid diethyl ester.
 17. A composition according to claim 1 wherein thecompound is2-amino-6-methyl-4-(4-methylmercaptophenyl)-1,4-dihydropyridine-3,5-dicarboxylic acid diethyl ester.
 18. A composition according to claim 1wherein the compound is2-amino-6-methyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylicacid 3-ethyl 5-isopropyl ester.
 19. A composition according to claim 1wherein the compound is2-amino-6-methyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylicacid 3-ethyl ester 5-propargyl ester.
 20. A composition according toclaim 1 wherein the compound is2-amino-6-methyl-4-(3-nitro-6-chlorophenyl)-1,4-dihydropyridine-3,5-dicarboxylic acid 3-ethyl ester 5-methyl ester.
 21. A compositionaccording to claim 1 wherein the compound is2-amino-6-methyl-4-(fur-2-yl)-1,4-dihydropyridine-3,5-dicarboxylic aciddiethyl ester.
 22. A composition according to claim 1 wherein thecompound is 2-amino-4,6-diphenyl-1,4-dihydropyridine-3,5-dicarboxylicacid ethyl ester.
 23. A composition according to claim 1 wherein thecompound is 2-amino-4,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylicacid diether ester.
 24. A composition according to claim 1 wherein thecompound is2-amino-4-methyl-1,4,5,6,7,8-hexahydro-5-oxoquinoline-3-carboxylic acidethyl ester.
 25. A composition according to claim 1 wherein the compoundis2-amino-4-(3-chlorophenyl)-1,4,5,6,7,8-hexahydro-5-oxoquinoline-3-carboxylicacid ethyl ester.
 26. A composition according to claim 1 wherein thecompound is 2-amino-4-( Alpha-pyridyl)-1,4,5,6,7,8-hexahydro-5-oxoquinoline-3-carboxylic acid ethylester.
 27. A composition according to claim 1 wherein the compound is2-amino-4-(quinol-4-yl)-1,4,5,6,7,8-hexahydro-5-oxoquinoline-carboxylicacid 3-ethyl ester.
 28. A composition according to claim 1 wherein thecompound is2-amino-4-(4,6-dimethoxypyrimid-5-yl)-1,4,5,6,7,8-hexahydro-5-oxoquinoline-3-carboxylicacid ethyl ester.
 29. A composition according to claim 1 wherein thecompound is2-amino-4-(naphth-l-yl)-1,4,5,6,7,8-hexahydro-5-oxoquinoline-3-carboxylicacid ethyl ester.
 30. A composition according to claim 1 wherein thecompound is2-amino-4-(isoquinol-l-yl)-1,4,5,6,7,8-hexahydro-5-oxoquinoline13-carboxylicacid ethyl ester.
 31. A composition according to claim 1 wherein thecompound is2-amino-4-(6-methylpyrid-2-yl)-1,4,5,6,7,8-hexahydro-5-oxoquinoline-3-carboxylic acid ethyl ester.
 32. A composition according to claim 1wherein the compound is2-amino-6-methyl-5-carbethoxy-4-(3-nitrophenyl)-1,4-dihydropyridine-3-carboxylic acid amide.
 33. A composition according to claim 1 whereinthe compound is2-amino-4-(2-cyanophenyl)-1,4,5,6,7,8-hexahydro-5-oxoquinoline-3-carboxylicacid ethyl ester.
 34. A composition according to claim 1 wherein thecompound is2-amino-6-methyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylicacid 3-isopropyl ester 5-ethyl ester.
 35. A composition according toclaim 1 wherein the compound is2-amino-6-methyl-4-(2-trifluoromethylphenyl)-1,4-dihydropyridine-3,5-dicarboxylic acid 3-isopropyl ester 5-ethyl ester.
 36. A compositionaccording to claim 1 wherein the compound is2-amino-6-methyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylicacid diisopropyl ester.
 37. A composition according to claim 1 whereinthe compound is2-amino-6-methyl-4-(2-cyanophenyl)-1,4-dihydropyridine-3,5-dicarboxylicacid 3-isopropyl ester 5ethyl ester.
 38. A composition according toclaim 1 wherein the compound is2-amino-6-methyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylicacid 3-isopropyl ester 5-methyl ester.
 39. A composition according toclaim 1 wherein the compound is2-amino-4-(2-trifluoromethyl-4-nitrophenyl)-1,4,5,6,7,8-hexahydro-5-oxoquinoline-3-carboxylic acid ethyl ester.
 40. A composition accordingto claim 1 wherein the compound is2-amino-6-methyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylicacid 3-n-propyl ester 5-ethyl ester.
 41. A composition according toclaim 1 wherein the compound is2-amino-4-(2-nitro-4,5-dimethoxyphenyl)-1,4,5,6,7,8-hexahydro-5-oxoquinoline-3-carboxylicacid ethyl ester.
 42. A composition according to claim 1 wherein thecompound is2-amino-6-methyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylicacid 3-( Beta -methoxyethyl) ester 5-ethyl ester.
 43. A compositionaccording to claim 1 wherein the compound is2-amino-4-(biphenyl-2-yl)1,4,5,6,7,8-hexahydro-5-oxoquinoline-3-carboxylicacid ethyl ester.
 44. A composition according to claim 1 wherein thecompound is2-amino-6-methyl-4-(1-naphthyl)-1,4-dihydropyridine-3,5-dicarboxylicacid diethyl ester.
 45. A composition according to claim 1 wherein thecompound is2-amino-6-methyl-4-(2-cyanophenyl)-1,4-dihydropyridine-3,5-dicarboxylicacid 3-isopropyl ester 5-methyl ester.
 46. A composition according toclaim 1 wherein the compound is2-amino-6-methyl-4-(2-cyanophenyl)-1,4-dihydropyridine-3,5-dicarboxylicacid 3-ethyl ester 5-methyl ester.
 47. A composition according to claim1 wherein the compound is2-amino-6-methyl-4-(biphenyl-2-yl)-1,4-dihydropyridine-3,5-dicarboxylicacid ethyl ester.
 48. A composition according to claim 1 wherein thecompound is2-amino-6-methyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylicacid 3-n-propyl ester 5-methyl ester.
 49. A composition according toclaim 1 wherein the compound is2-amino-6-methyl-4-(2-thenyl)-1,4-dihydropyridine-3,5-dicarboxylic aciddiethyl ester.
 50. A composition according to claim 1 wherein thecompound is2-amino-6-methyl-4-phenyl-5-(N,N-dimethylaminocarbonyl)-1,4-dihydropyridine-3-carboxylic acid amide.
 51. A composition according to claim 1 whereinthe compound is2-amino-6-methyl-4-phenyl-1,4-dihydropyridine-3,5-dicarboxylic acid3-ethyl ester 5-(N,N-dimethylamide).
 52. A composition according toclaim 1 wherein the compound is2-amino-6-methyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylicacid 3-isopropyl ester 5-ethyl ester.
 53. A composition according toclaim 1 wherein the compound is2-amidino-6-methyl-4-(2-nitrophenyl-1,4-dihydropyridine-3,5-dicarboxylicacid 3-isopropyl ester 5-methyl ester.
 54. A composition according toclaim 1 wherein the compound is2-amino-6-methyl-4-(2-cyanophenyl)-1,4-dihydropyridine-3,5-dicarboxylicacid 3-n-propyl ester 5-ethyl ester.
 55. A composition according toclaim 1 wherein the compound is2-amino-6-methyl-4(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylicacid 3-n-propyl ester 5-isopropyl ester.
 56. A composition according toclaim 1 wherein the compound is2-amino-4-(3-cyanophenyl)-1,4,5,6,7,8-hexahydro-5-oxoquinoline-3-carboxylicacid ethyl ester.
 57. A composition according to claim 1 wherein thecompound is2-amino-4-(3-bromophenyl)-1,4,5,6,7,8-hexahydro-5-oxoquinoline-3-carboxylicacid ethyl ester.
 58. A composition according to claim 1 wherein thecompound is2-amino-4-(2-bromphenyl)-1,4,5,6,7,8-hexahydro-5-oxoquinoline-3-carboxylicacid ethyl ester.
 59. A composition according to claim 1 wherein thecompound is2-amino-4-(3-carbethoxyphenyl)-1,4,5,6,7,8-hexahydro-5-oxoquinoline-3-carboxylic acid ethyl ester.
 60. A composition to claim 1 wherein thecompound is2-amino-4-(2-azidophenyl)-1,4,5,6,7,8-hexahydro-5-oxoquinoline-3-carboxylicacid ethyl ester.
 61. A method of effecting coronary vessel dilation inhumans and animals which comprises administering to such human or animalin need thereof a coronary vessel dilating amount of a compound of theformula:
 62. A method according to claim 61 wherein R1 is phenyl.
 63. Amethod according to claim 62 wherein R is naphthyl; phenyl; phenylsubstituted with from one to three substituents selected from the groupconsisting of lower alkyl, lower alkoxy, halogeno, nitro, cyano,trifluoromethyl, azido, carbo(lower alkoxy), lower alkylsulfonyl, loweralkylsulfinyl and lower alkylthio; or biphenyl.
 64. A method accordingto claim 63 wherein the compound is2-amino-6-methyl-4-phenyl-1,4-dihydropyridine-3,5-dicarboxylic aciddiethyl ester.
 65. A method according to claim 63 wherein the compoundis2-amino-6-methyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylicacid diethyl ester.
 66. A method according to claim 63 wherein thecompound is2-amino-6-methyl-4-(2-methoxyphenyl)-1,4-dihydropyridine-3,5-dicarboxylicacid diethyl ester.
 67. A method according to claim 63 wherein thecompound is2-amino-6-methyl-4-(2-cyanophenyl)-1,4-dihydropyridine-3,5-dicarboxylicacid diethyl ester.
 68. A method according to claim 63 wherein thecompound is2-amino-6-methyl-4-(2-trifluoromethylphenyl)-1,4-dihydropyridine-3,5-dicarboxylic acid diethyl ester.
 69. A method according to claim 63wherein the compound is2-amino-6-methyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylicacid diethyl ester.
 70. A method according to claim 63 wherein thecompound is2-amino-6-methyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylicacid 3-ethyl ester-5-methyl ester.
 71. A method according to claim 63wherein the compound is2-amino-6-methyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylicacid 3-ethyl ester-5-( Beta -methoxyethyl) ester.
 72. A method accordingto claim 61 wherein the compound is2-amino-6-methyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylicacid 3-ethyl ester 5-methyl ester.
 73. A method according to claim 61wherein the compound is2-amino-6-methyl-4-(2-methylphenyl)-1,4-dihydropyridine-3,5-dicarboxylicacid diethyl ester.
 74. A method according to claim 61 wherein thecompound is2-amino-6-methyl-4-(3-chlorophenyl)-1,4-dihydropyridine-3,5-dicarboxylicacid diethyl ester.
 75. A method according to claim 61 wherein thecompound is2-amino-6-methyl-4-(4-methylmercaptophenyl)-1,4-dihydropyridine-3,5-dicarboxylic acid diethyl ester.
 76. A method according to claim 61wherein the compound is2-amino-6-methyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylicacid 3-ethyl 5-isopropyl ester.
 77. A method according to claim 61wherein the compound is2-amino-6-methyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylicacid 3-ethyl ester 5-propargyl ester.
 78. A method according to claim 61wherein the compound is2-amino-6-methyl-4-(3-nitro-6-chlorophenyl)-1,4-dihydropyridine-3,5-dicarboxylic acid 3-ethyl ester 5-methyl ester.
 79. A method accordingto claim 61 wherein the compound is2-amino-6-methyl-4-(fur-2-yl)-1,4-dihydropyridine-3,5-dicarboxylic aciddiethyl ester.
 80. A method according to claim 61 wherein the compoundis 2-amino-4,6-diphenyl-1,4-dihydropyridine-3,5-dicarboxylic acid ethylester.
 81. A method according to claim 61 wherein the compound is2-amino-4,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylic acid diethylester.
 82. A method according to claim 61 wherein the compound is2-amino-4-methyl-1,4,5,6,7,8-hexahydro-5-oxoquinoline-3-carboxylic acidethyl ester.
 83. A method according to claim 61 wherein the compound is2-amino-4-(3-chlorophenyl)-1,4,5,6,7,8-hexahydro-5-oxoquinoline-3-carboxylicacid ethyl ester.
 84. A method according to claim 61 wherein thecompound is 2-amino-4-( Alpha-pyridyl)-1,4,5,6,7,8-hexahydro-5-oxoquinoline-3-carboxylic acid ethylester.
 85. A method according to claim 61 wherein the compound is2-amino-4-(quinol-4-yl)-1,4,5,6,7,8-hexahydro-5-oxoquinoline-carboxylicacid 3-ethyl ester.
 86. A method according to claim 61 wherein thecompound is2-amino-4-(4,6-dimethoxypyrimid-5-yl)-1,4,5,6,7,8-hexahydro-5-oxoquinoline-3-carboxylicacid ethyl ester.
 87. A method according to claim 61 wherein thecompound is2-amino-4-(naphth-1-yl)-1,4,5,6,7,8-hexahydro-5-oxoquinoline-3-carboxylicacid ethyl ester.
 88. A method according to claim 61 wherein thecompound is2-amino-4-(isoquinol-1-yl)-1,4,5,6,7,8-hexahydro-5-oxoquinoline-3-carboxylicacid ethyl ester.
 89. A method according to claim 61 wherein thecompound is2-amino-4-(6-methylpyrid-2-yl)-1,4,5,6,7,8-hexahydro-5-oxoquinoline-3-carboxylic acid ethyl ester.
 90. A method according to claim 61 whereinthe compound is2-amino-6-methyl-5-carbethoxy-4-(3-nitrophenyl)-1,4-dihydropyridine-3-carboxylic acid amide.
 91. A method according to claim 61 wherein thecompound is2-amino-4-(2-cyanophenyl)-1,4,5,6,7,8-hexahydro-5-oxoquinoline-3-carboxylicacid ethyl ester.
 92. A method according to claim 61 wherein thecompound is2-amino-6-methyl-4-(3-nitrophenyl))-1,4-dihydropyridine-3,5-dicarboxylicacid 3-isopropyl ester 5-ethyl ester.
 93. A method according to claim 61wherein the compound is2-amino-6-methyl-4-(2-trifluoromethylphenyl)-1,4-dihydropyridine-3,5-dicarboxylic acid 3-isopropyl ester 5-ethyl ester.
 94. A methodaccording to claim 61 wherein the compound is2-amino-6-methyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylicacid diisopropyl ester.
 95. A method according to claim 61 wherein thecompound is2-amino-6-methyl-4-(2-cyanophenyl)-1,4-dihydropyridine-3,5-dicarboxylicacid 3-isopropyl ester 5-ethyl ester.
 96. A method according to claim 61wherein the compound is2-amino-6-methyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylicacid 3-isopropyl ester 5-methyl ester.
 97. A method according to claim61 wherein the compound is2-amino-4-(2-trifluoromethyl-4-nitrophenyl)-1,4,5,6,7,8-hexahydro-5-oxoquinoline-3-carboxylic acid ethyl ester.
 98. A method according toclaim 61 wherein the compound is2-amino-6-methyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylicacid 3-n-propyl ester 5-ethyl ester.
 99. A method according to claim 61wherein the compound is2-amino-4-(2-nitro-4,5-dimethoxyphenyl)-1,4,5,6,7,8-hexahydro-5-oxoquinoline-3-carboxylicacid ethyl ester.
 100. A method according to claim 61 wherein thecompound is2-amino-6-methyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylicacid 3-( Beta -methoxyethyl) ester 5-ethyl ester.
 101. A methodaccording to claim 61 wherein the compound is2-amino-4-(biphenyl-2-yl)-1,4,5,6,7,8-hexahydro-5-oxoquinoline-3-carboxylicacid ethyl ester.
 102. A method according to claim 61 wherein thecompound is2-amino-6-methyl-4-(1-naphthyl)-1,4-dihydropyridine-3,5-dicarboxylicacid diethyl ester.
 103. A method according to claim 61 wherein thecompound is2-amino-6-methyl-4-(2-cyanophenyl)-1,4-dihydropyridine-3,5-dicarboxylicacid 3-isopropyl ester 5-methyl ester.
 104. A method according to claim61 wherein the compound is2-amino-6-methyl-4-(2-cyanophenyl)-1,4-dihydropyridine-3,5-dicarboxylicacid 3-ethyl ester 5-methyl ester.
 105. A method according to claim 61wherein the compound is2-amino-6-methyl-4-(biphenyl-2-yl)-1,4-dihydropyridine-3,5-dicarboxylicacid ethyl ester.
 106. A method according to claim 61 wherein thecompound is2-amino-6-methyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylicacid 3-n-propyl ester 5-methyl ester.
 107. A method according to claim61 wherein the compound is2-amino-6-methyl-4-(2-thenyl)-1,4-dihydropyridine-3,5-dicarboxylic aciddiethyl ester.
 108. A method according to claim 61 wherein the compoundis2-amino-6-methyl-4-phenyl-5-(N,N-dimethylaminocarbonyl)-1,4-dihydropyridine-3-carboxylic acid amide.
 109. A method according to claim 61 whereinthe compound is2-amino-6-methyl-4-phenyl-1,4-dihydropyridine-3,5-dicarboxylic acid3-ethyl ester (5-N,N-dimethylamide).
 110. A method according to claim 61wherein the compound is2-amino-6-methyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylicacid acid 3-isopropyl ester 5-ethyl ester.
 111. A method according toclaim 61 wherein the compound is2-amidino-6-methyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylicacid 3-isopropyl ester 5-methyl ester.
 112. A method according to claim61 wherein the compound is2-amino-6-methyl-4-(2-cyanophenyl)-1,4-dihydropyridine-3,5-dicarboxylicacid 3-n-propyl ester 5-ethyl ester.
 113. A method according to claim 61wherein the compound is2-amino-6-methyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylicacid 3-n-propyl ester 5-isopropyl ester.
 114. A method according toclaim 61 wherein the compound is2-amino-4-(3-cyanophenyl)-1,4,5,6,7,8-hexahydro-5-oxoquinoline3-carboxylic acid ethyl ester.
 115. A method according to claim 61wherein the compound is2-amino-4-(3-bromophenyl)-1,4,5,6,7,8-hexahydro-5-oxoquinoline-3-carboxylicacid ethyl ester.
 116. A method according to claim 61 wherein thecompound is2-amino-4-(2-bromophenyl)-1,4,5,6,7,8-hexahydro-5-oxoquinoline-3-carboxylicacid ethyl ester.
 117. A method according to claim 61 wherein thecompound is2-amino-4-(3-carbethoxyphenyl)-1,4,5,6,7,8-hexahydro-5-oxoquinoline-3-carboxylic acid ethyl ester.
 118. A method according to claim 61wherein the compound is2-amino-4-(2-azidophenyl)-1,4,5,6,7,8-hexahydro-5-oxoquinoline-3-carboxylicacid ethyl ester.
 119. A method of treating hypertension in humans andanimals which comprises administering to such human or animal in needthereof an antihypertensive amount of a compound of the formula:
 120. Amethod according to claim 119 wherein R1 is phenyl.
 121. A methodaccording to claim 120 wherein R is naphthyl; phenyl; phenyl substitutedwith from one to three substituents selected from the group consistingof lower alkyl, lower alkoxy, halogeno, nitro, cyano, trifluoromethyl,azido, carbo(lower alkoxy), lower alkylsulfonyl, lower alkylsulfinyl andlower alkylthio; or biphenyl.
 122. A method according to claim 121wherein the compound is2-amino-6-methyl-4-phenyl-1,4-dihydropyridine-3,5-dicarboxylic aciddiethyl ester.
 123. A method according to claim 121 wherein the compoundis2-amino-6-methyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylicacid diethyl ester.
 124. A method according to claim 121 wherein thecompound is2-amino-6-methyl-4-(2-methoxyphenyl)-1,4-dihydropyridine-3,5-dicarboxylicacid diethyl ester.
 125. A method according to claim 121 wherein thecompound is2-amino-6-methyl-4-(2-cyanophenyl)-1,4-dihydropyridine-3,5-dicarboxylicacid diethyl ester.
 126. A method according to claim 121 wherein thecompound is2-amino-6-methyl-4-(2-trifluoromethylphenyl)-1,4-dihydropyridine-3,5-dicarboxylic acid diethyl ester.
 127. A method according to claim 121wherein the compound is2-amino-6-methyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylicacid diethyl ester.
 128. A method according to claim 121 wherein thecompound is2-amino-6-methyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylicacid 3-ethyl ester-5-methyl ester.
 129. A method according to claim 121wherein the compound is2-amino-6-methyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylicacid 3-ethyl ester-5-( Beta -methoxyethyl) ester.
 130. A methodaccording to claim 119 wherein the compound is2-amino-6-methyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylicacid 3-ethyl ester 5-methyl ester.
 131. A method according to claim 119wherein the compound is2-amino-6-methyl-4-(2-methylphenyl)-1,4-dihydropyridine-3,5-dicarboxylicacid diethyl ester.
 132. A method according to claim 119 wherein thecompound is2-amino-6-methyl-4-(3-chlorophenyl)-1,4-dihydropyridine-3,5-dicarboxylicacid diethyl ester.
 133. A method according to claim 119 wherein thecompound is2-amino-6-methyl-4-(4-methylmercaptophenyl)-1,4-dihydropyridine-3,5-dicarboxylic acid diethyl ester.
 134. A method according to claim 119wherein the compound is2-amino-6-methyl-4-(3-nitrophenyl)-1,4-dihydropyriDine-3,5-dicarboxylicacid 3-ethyl 5-isopropyl ester.
 135. A method according to claim 119wherein the compound is2-amino-6-methyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylicacid 3-ethyl ester 5-propargyl ester.
 136. A method according to claim119 wherein the compound is2-amino-6-methyl-4-(3-nitro-6-chlorophenyl)-1,4-dihydropyridine-3,5-dicarboxylic acid 3-ethyl ester 5-methyl ester.
 137. A methodaccording to claim 119 wherein the compound is2-amino-6-methyl-4-(fur-2-yl)-1,4-didhydropyridine-3,5-dicarboxylic aciddiethyl ester.
 138. A method according to claim 119 wherein the compoundis 2-amino-4,6-diphenyl-1,4-dihydropyridine-3,5-dicarboxylic acid ethylester.
 139. A method according to claim 119 wherein the compound is2-amino-4,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylic acid diethylester.
 140. A method according to claim 119 wherein the compound is2-amino-4-methyl-1,4,5,6,7,8-hexahydro-5-oxoquinoline-3-carboxylic acidethyl ester.
 141. A method according to claim 119 wherein the compoundis2-amino-4-(3-chlorophenyl)-1,4,5,6,7,8-hexahydro-5-oxoquinoline-3-carboxylicacid ethyl ester.
 142. A method according to claim 119 wherein thecompound is 2-amino-4-( Alpha-pyridyl)-1,4,5,6,7,8-hexahydro-5-oxoquinoline-3-carboxylic acid ethylester.
 143. A method according to claim 119 wherein the compound is2-amino-4-(quinol-4-yl)-1,4,5,6,7,8-hexahydro-5-oxoquinoline-carboxylicacid 3-ethyl ester.
 144. A method according to claim 119 wherein thecompound is2-amino-4-(4,6-dimethoxypyrimid-5-yl)-1,4,5,6,7,8-hexahydro-5-oxoquinoline-3-carboxylicacid ethyl ester.
 145. A method according to claim 119 wherein thecompound is2-amino-4-(naphth-1-yl)-1,4,5,6,7,8-hexahydro-5-oxoquinoline-3-carboxylicacid ethyl ester.
 146. A method according to claim 119 wherein thecompound is2-amino-4-(isoquinol-1-yl)-1,4,5,6,7,8-hexahydro-5-oxoquinoline-3-carboxylicacid ethyl ester.
 147. A method according to claim 119 wherein thecompound is2-amino-4-(6-methylpyrid-2-yl)-1,4,5,6,7,8-hexahydro-5-oxoquinoline-3-carboxylic acid ethyl ester.
 148. A method according to claim 119wherein the compound is2-amino-6-methyl-5-carbethoxy-4-(3-nitrophenyl)-1,4-dihydropyridine-3-carboxylic acid amide.
 149. A method according to claim 119 wherein thecompound is2-amino-4-(2-cyanophenyl)-1,4,5,6,7,8-hexahydro-5-oxoquinoline-3-carboxylicacid ethyl ester.
 150. A method according to claim 119 wherein thecompound is2-amino-6-methyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylicacid 3-isopropyl ester 5-ethyl ester.
 151. A method according to claim119 wherein the compound is2-amino-6-methyl-4-(2-trifluoromethylphenyl)-1,4-dihydropyridine-3,5-dicarboxylic acid 3-isopropyl ester 5-ethyl ester.
 152. A methodaccording to claim 119 wherein the compound is2-amino-6-methyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylicacid diisopropyl ester.
 153. A method according to claim 119 wherein thecompound is2-amino-6-methyl-4-(2-cyanophenyl)-1,4-dihydropyridine-3,5-dicarboxylicacid 3-isopropyl ester 5-ethyl ester.
 154. A method according to claim119 wherein the compound is2-amino-6-methyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylicacid 3-isopropyl ester 5-methyl ester.
 155. A method according to claim119 wherein the compound is2-amino-4-(2-trifluoromethyl-4-nitrophenyl)-1,4,5,6,7,8-hexahydro-5-oxoquinoline-3-carboxylic acid ethyl ester.
 156. A method according toclaim 119 wherein the compound is2-amino-6-methyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylicacid 3-n-propyl ester 5-ethyl ester.
 157. A method according to claim119 wherein the compound is2-amino-4-(2-nitro-4,5-dimethoxyphenyl)-1,4,5,6,7,8-hexahydro-5-oxoquinoline-3-carboxylicacid ethyl ester.
 158. A method according to claim 119 wherein thecompound is2-amino-6-methyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylicacid 3-( Beta -methoxyethyl) ester 5-ethyl ester.
 159. A methodaccording to claim 119 wherein the compound is2-amino-4-(biphenyl-2-yl)-1,4,5,6,7,8-hexahydro-5-oxoquinoline-3-carboxylicacid ethyl ester.
 160. A method according to claim 119 wherein thecompound is2-amino-6-methyl-4-(1-naphthyl)-1,4-dihydropyridine-3,5-dicarboxylicacid diethyl ester.
 161. A method according to claim 119 wherein thecompound is2-amino-6-methyl-4-(2-cyanophenyl)-1,4-dihydropyridine-3,5-dicarboxylicacid 3-isopropyl ester 5-methyl ester.
 162. A method according to claim119 wherein the compound is2-amino-6-methyl-4-(2-cyanophenyl)-1,4-dihydropyridine-3,5-dicarboxylicacid 3-ethyl ester 5-methyl ester.
 163. A method according to claim 119wherein the compound is2-amino-6-methyl-4-(biphenyl-2-yl)-1,4-dihydropyridine-3,5-dicarboxylicacid ethyl ester.
 164. A method according to claim 119 wherein thecompound is2-amino-6-methyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylicacid 3-n-propyl ester 5-methyl ester.
 165. A method according to claim119 wherein the compound is2-amino-6-methyl-4-(2-thenyl)-1,4-dihydropyridine-3,5-dicarboxylic aciddiethyl ester.
 166. A method according to claim 119 wherein the compoundis2-amino-6-methyl-4-phenyl-5-(N,N-dimethylaminocarbonyl)-1,4-dihydropyridine-3-carboxylic acid amide.
 167. A method according to claim 119 whereinthe compound is2-amino-6-methyl-4-phenyl-1,4-dihydropyridine-3,5-dicarboxylic acid3-ethyl ester (5-N,N-dimethylamide).
 168. A method according to claim119 wherein the compound is2-amino-6-methyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylicacid acid 3-isopropyl ester 5-ethyl ester.
 169. A method according toclaim 119 wherein the compound is2-amidino-6-methyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylicacid 3-isopropyl ester 5-methyl ester.
 170. A method according to claim119 wherein the compound is2-amino-6-methyl-4-(2-cyanophenyl)-1,4-dihydropyridine-3,5-dicarboxylicacid 3-n-propyl ester 5-ethyl ester.
 171. A method according to claim119 wherein the compound is2-amino-6-methyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylicacid 3-n-propyl ester 5-isopropyl ester.
 172. A method according toclaim 119 wherein the compound is2-amino-4-(3-cyanophenyl)-1,4,5,6,7,8-hexahydro-5-oxoquinoline3-carboxylic acid ethyl ester.
 173. A method according to claim 119wherein the compound is2-amino-4-(3-bromophenyl)-1,4,5,6,7,8-hexahydro-5-oxoquinoline-3-carboxylicacid ethyl ester.
 174. A method according to claim 119 wherein thecompound is2-amino-4-(2-bromophenyl)-1,4,5,6,7,8-hexahydro-5-oxoquinoline-3-carboxylicacid ethyl ester.
 175. A method according to claim 119 wherein thecompound is2-amino-4-(3-carbethoxyphenyl)-1,4,5,6,7,8-hexahydro-5-oxoquinoline-3-carboxylic acid ethyl ester.
 176. A method according to claim 119wherein the compound is2-amino-4-(2-azidophenyl)-1,4,5,6,7,8-hexahydro-5-oxoquinoline-3-carboxylicacid ethyl ester.